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    You are here : Home » MS Research News » Stem Cell Research & Treatment » MS Specific Stem Cell Research & Treatment

    MS Specific Stem Cell Research & Treatment

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    Haematopoietic Stem Cell Transplantation (HSCT) Blogs

    Follow the progress of MSers undergoing HSCT to treat their Multiple Sclerosis

    The Myelin Repair Foundation achieves phase 1 myelin repair clinical trial

    Stem cellsThe Myelin Repair Foundation (MRF) today announced the achievement of a myelin repair Phase 1 clinical trial for multiple sclerosis earlier than the foundation's goal set for 2014. By establishing its Accelerated Research Collaboration (ARC) Model to advance myelin repair treatments forward into clinical trial Phase 1 within a decade, the Myelin Repair Foundation achieved this critical milestone ahead of its goal, validating the efficiency of the ARC model to speed drug development.

    This Phase 1 clinical trial conducted at Cleveland Clinic will examine the efficacy of a new myelin repair therapeutic pathway with mesenchymal stem cells (MSCs), based on MRF supported research conducted by MRF Principal Investigator Dr. Robert Miller, Professor of Neurosciences and Vice President for Research & Technology Management at Case Western Reserve University. To date, half of the 24 patients planned for this initial trial have been enrolled.

    "Scientists hope that one day their research will reach clinical trials, and I'm thrilled to achieve this milestone in my career," said Dr. Robert Miller. "Without the support of Myelin Repair Foundation funding a critical component of our research that is the basis of this trial, this achievement would not have been possible. Our partnership with the Myelin Repair Foundation has helped identify new pathways to treat disease that reverses damage, ultimately accomplishing so much more than the suppression of MS symptoms."

    Funded by the Myelin Repair Foundation, Dr. Miller's team of scientists identified an innovative clinical pathway through mesenchymal stem cell signals that not only protect myelin, which is damaged by the autoimmune reaction in MS, but also facilitates myelin repair. Current MS drugs on the market only focus on the suppression of the immune system to protect myelin from future damage; patients have no treatment options available to repair myelin once damage occurs in MS.

    "Our goal to support research that would enter Phase 1 trials within a decade was deemed nearly impossible," said Scott Johnson, president and CEO of the Myelin Repair Foundation. "To think we achieved this ambitious goal even earlier than we planned illustrates the effectiveness of our innovative research model that accelerates promising scientific discoveries into clinical trials. Even with this success, we refuse to rest on our laurels and will continue to progress myelin research into multiple clinical trials. We remain focused on our singular goal: To speed the development of an effective myelin repair treatment to reach patients with multiple sclerosis."

    For more information about the clinical trial and enrollment, please visit http://www.clinicaltrials.gov/ .

    About the Myelin Repair Foundation

    The Myelin Repair Foundation (MRF) is a Silicon Valley-based, non-profit research organization focused on accelerating the discovery and development of myelin repair therapeutics for multiple sclerosis. Its Accelerated Research Collaboration(TM) (ARC(TM)) model is designed to optimize the entire process of medical research, drug development and the delivery of patient treatments.

    Source: MarketWatch Copyright © 2012 MarketWatch, Inc (15/06/12

    Immunologist to create new line of neural stem cells for MS

    Stem CellsA UC Irvine immunologist will receive $4.8 million to create a new line of neural stem cells that can be used to treat multiple sclerosis.

    The California Institute for Regenerative Medicine awarded the grant Thursday, May 24, to Thomas Lane of the Sue & Bill Gross Stem Cell Research Center at UCI to support early-stage translational research.

    CIRM's governing board gave 21 such grants worth $69 million to 11 institutions statewide. The funded projects are considered critical to the institute's mission of translating basic stem cell discoveries into clinical cures. They are expected to either result in candidate drugs or cell therapies or make significant strides toward such treatments, which can then be developed for submission to the Food & Drug Administration for clinical trial.

    Lane's grant brings total CIRM funding for UCI to $76.65 million.

    "I am delighted that CIRM has chosen to support our efforts to advance a novel stem cell-based therapy for multiple sclerosis," said Peter Donovan, director of the Sue & Bill Gross Stem Cell Research Center.

    MS is a disease of the central nervous system caused by inflammation and loss of myelin, a fatty tissue that insulates and protects nerve cells. Current treatments are often unable to stop the progression of neurologic disability - most likely due to irreversible nerve destruction resulting from myelin deficiencies. The limited ability of the body to repair damaged nerve tissue highlights a critically important and unmet need for MS patients.

    In addressing this issue, Lane - who also directs UCI's Multiple Sclerosis Research Center - will target a stem cell treatment that will not only halt ongoing myelin loss but also encourage the growth of new myelin that can mend damaged nerves.

    "Our preliminary data are very promising and suggest that this goal is possible," said Lane, a Chancellor's Fellow and professor of molecular biology & biochemistry. "Research efforts will concentrate on refining techniques for production and rigorous quality control of transplantable cells generated from high-quality human pluripotent stem cell lines, leading to the development of the most therapeutically beneficial cell type for eventual use in patients with MS."

    The best estimates indicate that there are 400,000 people diagnosed with MS in the U.S., with nearly half - about 160,000 - living in California. The economic, social and medical costs associated with the disease are in the billions of dollars, placing a significant burden on the state's healthcare system.

    As an MS patient and research advocate, Nan Luke sees support for Lane's work as a positive step toward a regenerative therapy. The Irvine attorney was diagnosed with MS more than 20 years ago, and current treatments have slowed its progress but cannot undo damage to critical areas of her brain.

    "This new research gives me and others like me real hope that our nerve damage may be repaired and that we may regain lost function," said Luke, who serves on the Sue & Bill Gross Stem Cell Research Center's patient advocacy committee.

    Lane will collaborate with Australian MS researcher Claude Bernard at Monash University in Melbourne, who will help validate the cell line's effectiveness. Australia's National Health & Medical Research Council will provide a supplemental $1.8 million as part of CIRM's new collaborative funding program.

    Additionally, Jeanne Loring, director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla, will work with Lane to develop the neural stem cells to be used in the study.

    Source: NewsMedical.net (28/05/12)

    Growth factor in stem cells may spur recovery from multiple sclerosis

    Stem CellsA substance in human mesenchymal stem cells that promotes growth appears to spur restoration of nerves and their function in rodent models of multiple sclerosis (MS), researchers at Case Western Reserve University School of Medicine have found.

    Their study appeared in the online version of Nature Neuroscience on Sunday, May 20.

    In animals injected with hepatocyte growth factor, inflammation declined and neural cells grew. Perhaps most important, the myelin sheath, which protects nerves and their ability to gather and send information, regrew, covering lesions caused by the disease.

    "The importance of this work is we think we've identified the driver of the recovery," said Robert H. Miller, professor of neurosciences at the School of Medicine and vice president for research at Case Western Reserve University.

    Miller, neurosciences instructor Lianhua Bai and biology professor Arnold I. Caplan, designed the study. They worked with Project Manager Anne DeChant, and research assistants Jordan Hecker, Janet Kranso and Anita Zaremba, from the School of Medicine; and Donald P. Lennon, a research assistant from the university's Skeletal Research Center.

    In MS, the immune system attacks myelin, risking injury to exposed nerves' intricate wiring. When damaged, nerve signals can be interrupted, causing loss of balance and coordination, cognitive ability and other functions. Over time, intermittent losses may become permanent.

    Miller and Caplan reported in 2009 that when they injected human mesenchymal stem cells into rodent models of MS, the animals recovered from the damage wrought by the disease. Based on their work, a clinical trial is underway in which MS patients are injected with their own stem cells.

    In this study, the researchers first wanted to test whether the presence of stem cells or something cells produce promotes recovery. They injected mice with the medium in which mesenchymal stem cells, culled from bone marrow, grew.

    All 11 animals, which have a version of MS, showed a rapid reduction in functional deficits.

    Analysis showed that the disease remained on course unless the molecules injected were of a certain size; that is, the molecular weight ranged between 50 and 100 kiloDaltons.

    Research by others and results of their own work indicated hepatocyte growth factor, which is secreted by mesenchymal stem cells, was a likely instigator.

    The scientists injected animals with 50 or 100 nanograms of the growth factor every other day for five days. The level of signaling molecules that promote inflammation decreased while the level of signaling molecules that counter inflammation increased. Neural cells grew and nerves laid bare by MS were rewrapped with myelin. The 100-nanogram injections appeared to provide slightly better recovery.

    To test the system further, researchers tied up cell-surface receptors, in this case cMet receptors that are known to work with the growth factor.

    When they jammed the receptors with a function-blocking cMet antibody, neither the mesenchymal stem cell medium nor the hepatocyte growth factor injections had any effect on the disease. In another test, injections of an anti-hepatocyte growth factor also blocked recovery.

    The researchers will continue their studies, to determine if they can screen mesenchymal stem cells for those that produce the higher amounts of hepatocyte growth factor needed for effective treatment. That could lead to a more precise cell therapy.

    "Could we now take away the mesenchymal stem cells and treat only with hepatocyte growth factor?" Miller asked. "We've shown we can do that in an animal but it's not clear if we can do that in a patient."

    They also plan to test whether other factors may be used to stimulate the cMet receptors and induce recovery.

    Source: Medical Xpress © Medical Xpress 2011-2012 (21/05/12)

    Potential new myelin repair treatment for Multiple Sclerosis

    Stemcells The Myelin Repair Foundation (MRF) today announced the results of a new peer-reviewed research study published in Nature Neuroscience that demonstrates functional improvement in immune response modulation and myelin repair with factors derived from mesenchymal stem cell (MSC) treatment in animal models of multiple sclerosis (MS).

    Funded by the Myelin Repair Foundation, this research conducted by Case Western Reserve University scientists showed positive results with human mesenchymal stem cells in animal models of MS by not only successfully blocking the autoimmune MS response, but also repairing myelin, demonstrating an innovative potential myelin repair treatment for MS.

    Multiple sclerosis is a disease of the immune system that attacks the myelin, causing exposed nerves or "lesions" which block brain signals, causing loss of motor skills, coordination and cognitive ability. Compared to the controls, this research study showed fewer and smaller lesions found on the nerves in the MSC treatment group. MSCs were found to block the formation of scar tissue by suppressing the autoimmune response, which would otherwise cause permanent damage to the nerves. Furthermore, the research showed that MSC treatment also repaired myelin, enhancing myelin regeneration of the damaged axon and the rewrapping of the myelin around the axon in animal models of MS. One treatment of MSCs provided long-term protection of the recurring disease.

    Led by Myelin Repair Foundation Principal Investigator and Vice President for Research & Technology Management at Case Western Reserve University's Dr. Robert Miller, this study documents a new promising pathway for treating multiple sclerosis that blocks the autoimmune response and reverses the myelin damage in animal models of MS. The human MSCs used in this study were culled from adult stem cells derived from the bone marrow.

    "We are thrilled with the publication of this important research study that examines a new pathway to treat multiple sclerosis, one that reverses the damage of the disease," said Dr. Robert Miller. "Since we were just beginning to understand how MSCs provide myelin repair for lesions, with the Myelin Repair Foundation's support, we continue to deepen our knowledge of exploring the next generation of MS treatments that stimulate healing, rather than symptom suppression of the disease."

    "We pride ourselves on supporting best-in-class scientists devoted to find new ways to treat multiple sclerosis, advancing highly innovative research projects that otherwise would not have moved forward," said Scott Johnson, president of the Myelin Repair Foundation. "The success of Case Western Reserve University's study and recognition in this prestigious journal furthers our goal to identify new pathways to treat multiple sclerosis by supporting a multi-disciplinary team of the best researchers in the field."

    About the Myelin Repair Foundation

    The Myelin Repair Foundation (MRF) is a Silicon Valley-based, non-profit research organization focused on accelerating the discovery and development of myelin repair therapeutics for multiple sclerosis. Its Accelerated Research Collaboration(TM) (ARC(TM)) model is designed to optimize the entire process of medical research, drug development and the delivery of patient treatments.

    Source: MarketWatch Copyright © 2012 MarketWatch, Inc (21/05/12)

    Stemcell hope for multiple sclerosis

    Stem CellsStemcell therapy for multiple sclerosis is now a reality, not just a dream, says a leading neuro-immunologist.

    Gianvito Martino, director of neuroscience at San Raffaele Hospital in Milan, Italy, said although the therapy was still experimental, it was yielding some exciting results.

    Professor Martino said he did not believe stemcell therapy would be the solution to MS but an important treatment option with fewer side effects.

    "To have the solution, we should know the cause of the disease but we don't know it," he said.

    About 85 per cent of patients had relapsing remitting MS, which could be managed with current treatments, he said. However, within 10-20 years, about 90 per cent of these patients moved into the secondary progressive phase, for which there were no effective treatments, while about 10 per cent continued to have the so-called benign first phase.

    "About 80-85 per cent of patients will need aid for walking in 20-25 years from diagnosis," he said.

    The average age of diagnosis is 20-40. In Australia, three times as many females are affected. In the autoimmune disease, the insulating sheath of the nerve cells, called myelin, is attacked and destroyed and eventually the nerves are also destroyed, leading to progressive atrophy of the brain and spinal cord, which is the cause of disability. In Australia, the incidence of MS is about one in every 1000 people, with more than 21,000 people affected.

    Professor Martino said there were two types of stemcells already being used in patients, both from blood. They were haematopoietic and mesenchymal stemcells.

    Haematopoietic stemcells were those used in bone-marrow transplantations. The patient's immune system was destroyed by chemotherapy and then their own stemcells from the bone marrow were transplanted.

    "The idea is to have new blood with no more cells capable of damaging your myelin," Professor Martino said.

    "It is immuno- suppressive therapy, blocking the cells causing the disease."

    About 500 MS patients worldwide had received the therapy since 1997 and in many, the progression of their disease had been halted.

    "The results are very, very important because about 60 per cent of those patients do not worsen for up to four to five years after the transplants, they stabilise," Professor Martino said.

    Even more exciting was the fact that only the patients with the worst prognosis and unresponsive to approved therapies had been eligible for the treatment, which was proving so successful.

    Among those patients, the ones better responding to the transplant were the 5 per cent with the so-called malignant form of MS, who needed a wheelchair within five years of diagnosis.

    The second type of transplant used mesenchymal cells, which are multi-potent stemcells taken from the blood and which can differentiate into a variety of cell types.

    "They seem to help the immune system to block the body's reaction against itself," Professor Martino said. "You can just inject them intravenously and you don't need immuno-suppression or any therapy to avoid rejection."

    While they seemed to block further damage from the disease, they did not repair nerve cells already damaged.

    Apart from blood stemcells, there is another form of stemcell therapy which his group is testing, using neural stemcells taken from a foetus and grown in vitro as precursors of brain cells, which are then transplanted via a lumbar puncture.

    "Those cells were not only able to become cells producing myelin once transplanted but they could also help cells resident within the brain, which were not damaged by the disease, to repair the brain," he said.

    The trials conducted by his group to date have been in mice and monkeys. "We hope to start treatment in patients . . . within the next five years," he said.

    He warned MS patients against going to the so-called stemcell clinics that were scattered worldwide, saying the therapy should be conducted only under rigorous clinical trial conditions.

    Source: 'The West Australian' (c) West Australian Newspapers Limited 2012 (05/04/12)

    Autologous mesenchymal stem cells for the treatment of secondary progressive MS

    StemcellsAbstract

    BACKGROUND: More than half of patients with multiple sclerosis have progressive disease characterised by accumulating disability. The absence of treatments for progressive multiple sclerosis represents a major unmet clinical need. On the basis of evidence that mesenchymal stem cells have a beneficial effect in acute and chronic animal models of multiple sclerosis, we aimed to assess the safety and efficacy of these cells as a potential neuroprotective treatment for secondary progressive multiple sclerosis.

    METHODS: Patients with secondary progressive multiple sclerosis involving the visual pathways (expanded disability status score 5·5-6·5) were recruited from the East Anglia and north London regions of the UK. Participants received intravenous infusion of autologous bone-marrow-derived mesenchymal stem cells in this open-label study. Our primary objective was to assess feasibility and safety; we compared adverse events from up to 20 months before treatment until up to 10 months after the infusion. As a secondary objective, we chose efficacy outcomes to assess the anterior visual pathway as a model of wider disease. Masked endpoint analyses was used for electrophysiological and selected imaging outcomes. We used piecewise linear mixed models to assess the change in gradients over time at the point of intervention. This trial is registered with ClinicalTrials.gov, number NCT00395200.

    FINDINGS: We isolated, expanded, characterised, and administered mesenchymal stem cells in ten patients. The mean dose was 1·6×10(6) cells per kg bodyweight (range 1·1-2·0). One patient developed a transient rash shortly after treatment; two patients had self-limiting bacterial infections 3-4 weeks after treatment. We did not identify any serious adverse events. We noted improvement after treatment in visual acuity (difference in monthly rates of change -0·02 logMAR units, 95% CI -0·03 to -0·01; p=0·003) and visual evoked response latency (-1·33 ms, -2·44 to -0·21; p=0·020), with an increase in optic nerve area (difference in monthly rates of change 0·13 mm(2), 0·04 to 0·22; p=0·006). We did not identify any significant effects on colour vision, visual fields, macular volume, retinal nerve fibre layer thickness, or optic nerve magnetisation transfer ratio.

    INTERPRETATION: Autologous mesenchymal stem cells were safely given to patients with secondary progressive multiple sclerosis in our study. The evidence of structural, functional, and physiological improvement after treatment in some visual endpoints is suggestive of neuroprotection.

    FUNDING: Medical Research Council, Multiple Sclerosis Society of Great Britain and Northern Ireland, Evelyn Trust, NHS National Institute for Health Research, Cambridge and UCLH Biomedical Research Centres, Wellcome Trust, Raymond and Beverly Sackler Foundation, and Sir David and Isobel Walker Trust.

    Source: Lancet Neurol. 2012 Jan 9 Copyright © 2012 Elsevier Ltd & Pubmed PMID 22236384 (18/01/12)

    Scientists grow neurons that integrate into brain

    Stem CellsAustralian researchers have developed the world's first stem cell model of multiple sclerosis, opening up new ways to study the disease and test treatments.

    The deputy director of Monash University's immunology and stem cell laboratory, Claude Bernard, said he and his colleagues had used skin cells from MS sufferers to create induced pluripotent stem cells that have the capacity to become brain cells targeted by the disease.

    This effectively creates a ''disease in a dish'' that can be replicated and studied by researchers who have previously had only blood cells, autopsy tissue and cerebrospinal fluid to work on. The cells also mean scientists can avoid using human embryos, overcoming ethical concerns.

    Professor Bernard said this would create a limitless supply of the cells for researchers to study the mechanisms of the disease and to test new drugs.

    ''Much research to date has relied on animal models that, while similar to MS, have been very different to the human disease, which has led to ineffective and even detrimental MS treatments,'' he said.

    MS is the most common chronic neurological disease in the world and affects about 21,000 Australians.

    Given there is no cure and treatments work for only about 30 per cent of sufferers, Professor Bernard said it was critical to continue the research. ''There are so many people suffering from this difficult disease and it costs Australia about $2 billion a year.''

    The findings were published in Stem Cell Research.

    Source: The Sydney Morning Herald Copyright © 2011 Fairfax Media (21/12/11)

    MS bone marrow stem cell trial to begin

    Stem CellsBritish doctors are to conduct a trial using bone marrow stem cells that they hope could halt or perhaps even reverse the progression of multiple sclerosis (MS).

    The Bristol University team wants to recruit 80 people for the research, after a pilot study in six people showed "tantalising" results.

    The technique involves harvesting bone marrow from the patient, filtering out the stem cells and then injecting them into the person's veins the same day.

    The theory is that the stem cells help repair damage caused to the protective coating of nerve cells, called myelin, which is the cause of MS.

    Results from the safety study, published last year in the journal Clinical Pharmacology and Therapeutics, raised what researchers described as "the possibility of benefit".

    Professor Neil Scolding said at the time: "We are encouraged by the results of this early study.

    "The safety data are reassuring and the suggestion of benefit tantalising."

    However, the results showed no actual improvement in disease. Prof Scolding said a larger study was needed.

    The experimental approach is also controversial because some clinics outside Britain are charging thousands for it, before studies such as Prof Scolding's prove its effectiveness.

    Last year the MS Society said one such clinic, the XCell-Center in Germany, was "marketing unproven treatments".

    Now, following a £700,000 donation from an American charity, Bristol University and Frenchay Hospital hope to begin the clinical trial in February.

    About 100,000 people in Britain suffer from MS, in which nerve damage leads to symptoms including sight problems and difficulty walking.

    Prof Scolding said: "We are very excited by this as it will be the first trial of any repair therapy in MS, not only in the UK but anywhere."

    *Paper: Safety and feasibility of autologous bone marrow cellular therapy in relapsing-progressive multiple sclerosis, CM Rice, EA Mallam, AL Whone, P Walsh, DJ Brooks, N Kane, SR Butler, DI Marks and NJ Scolding, Clinical Pharmacology & Therapeutics advance online publication, 5 May 2010 (DOI 10.1038/sj.clpt. 12-09-0672.R2).

    Source: The Telegraph © Copyright of Telegraph Media Group Limited 2011 (05/12/11)

    Stem cell promise for multiple sclerosis

    Stem CellsNew research has found a way to replenish the fatty layer or myelin sheath around nerve cells1 — a finding that could yield a cure for neurodegenerative diseases such as multiple sclerosis.

    Researchers have now understood how the right mix of biological growth factors coaxes human embryonic stem cells (ESCs) to form oligodendrocytes, a type of nerve cells that form the myelin sheath.

    "We have been able to identify the proteins that are expressed during the differentiation of ESCs into oligodendrocyte progenitor cells, which in turn grow into oligodenrocytes," says Akhilesh Pandey, one of the researchers from the Institute of Bioinformatics, Bangalore and Johns Hopkins University School of Medicine, US. "We have also identified several proteins that aid the formation of myelin," he adds.

    Oligodendrocytes (OLs) are specialized cells that wrap tightly around axons to form the myelin sheath. The job of these support cells is to speed up the electrical signal that travels down an axon. Without oligodendrocytes an action potential would travel down an axon 30 times slower. Injury to OLs seems to initiate multiple sclerosis. Studies have also shown that OL injury has a role to play in schizophrenia.

    The best way to treat such disorders is to replace the worn-out OLs. To achieve this, studies have tried to grow OLs in lab. Oligodendrocyte progenitor cells (OPCs) have been grown from human ESCs in animals with spinal cord injury and multiple sclerosis. Lab studies have discovered a number of growth factors, which promote OPC migration, survival and proliferation. Despite identifying factors that affect OPC proliferation and differentiation, researchers knew little about the factors that trigger myelin-forming OLs.

    To zero in on proteins specific to OL differentiation, the researchers grew human ESCs in a nutrient broth laced with various growth factors. They observed the proliferation and differentiation of ESCs into embryoid bodies, neural progenitor cells (NPCs), glial progenitor cells (GPCs) and OPCs which could finally grow into OLs and form myelin. At every stage of cell differentiation, the researchers harvested cells and identified stage-specific proteins using state-of-the-art mass spectrometry analysis.

    The study identified 3145 proteins at key stages of OL differentiation from human ESCs. Some of the vital proteins at the OPC stage were neural cell adhesion molecule 1 (NCAM1), APOE, tenascin C (TNC), vimentin (VIM), wingless-related MMTV integration site 5A (WNT5A), and heat shock 27 kDa protein 1.

    "Further exploration of these proteins within the OL lineage is likely to yield novel therapies for diagnosing and treating many OL-associated or demyelinating conditions," Pandey says.

    The study also found novel markers for NPCs and GPCs which would add to the repertoire of specific markers increasing specificity. The NPCs can differentiate in neural and glial cells. "The multiple markers will aid in selection of pure cells, which is currently a limiting factor", Pandey adds.

    There is no single specific marker for a stem cell. "The study affords a group of protein markers for the identification of a cell type. Such identification will provide valuable clues for future studies about the pathways involved in the transformation of the ESCs into progenitor cells," says Sumantra Das who studies neurobiochemistry and neuropharmacology at Indian Institute of Chemical Biology, Kolkata.

    Though the study identifies molecular markers in a single shot, the question is how far the information is valuable since artificial progenitor cells generated may not be phenotypically similar to a primary progenitor cell isolated from the brain, Das says.

    "The study offers a comprehensive base line molecular data in normal embryonic stem cells and pluripotent neural, glial and oligodendroglial cells in a culture medium," says S. K. Shankar from the National Institute of Mental Health and Neuro Sciences, Bangalore. However, similar information in an animal system and isolation of cells at different lineages from intact organ are important for extrapolation, Shankar told Nature India.

    The authors of this study are from: Johns Hopkins University School of Medicine, Baltimore and University of Pennsylvania, Philadelphia, USA; Amrita School of Biotechnology, Amrita Viswa Vidyapeetham, Kollam, Kerala and Manipal University, India; Thermo Fisher Scientific (Bremen) GmbH, Bremen, Germany.

    References
    Chaerkady, R. et al. Quantitative temporal proteomic analysis of human embryonic stem cell differentiation into oligodendrocyte progenitor cells. Proteomics. 11, 4007-4020 (2011)

    Source: Nature India © 2011 Nature Publishing Group (01/12/11)

    MSRCNY receives approval for groundbreaking stem cell trial in MS

    Stem CellsLandmark Study Targets Repair and Regeneration for MS Patients

    The Multiple Sclerosis Research Center of New York (MSRCNY) and the International Cellular Medicine Society (ICMS) jointly announced today the ICMS Institutional Review Board's (IRB) approval of the first study to use autologous brain-like or neural stem cells for multiple sclerosis.

    "We are entering a whole new world of possibilities for our patients" said Dr. Saud A. Sadiq, Neurologist and Director of the MSRCNY. "This initial stem cell treatment strategy opens up new avenues of treatment options focused on repair and regeneration that didn't exist before." Dr. Sadiq added, "We are delighted that the ICMS has approved our study and feel both the MSRCNY and the ICMS share the basic ideology of advancing safe and effective treatment in addressing patient needs."

    The landmark study investigates a regenerative strategy using mesenchymal stem cell-derived neural progenitor cells harvested from the patient's own bone marrow. These stem cells will be injected into the cerebral spinal fluid surrounding the spinal cord in 20 participants with a confirmed diagnosis of progressive MS. This will be an open label safety and tolerability study where all participants will be enrolled through the Multiple Sclerosis Research Center of New York (MSRCNY). All study activities will be conducted at the MSRCNY and affiliated International Multiple Sclerosis Management Practice (IMSMP).

    Participants in the three year study will undergo a single bone marrow collection procedure, from which the neural progenitor cells will be isolated, expanded and tested prior to injection. Participants will undergo three rounds of injections at three month intervals. Safety and efficacy parameters will be evaluated in all participants through scheduled follow-up visits.

    MS is a chronic human autoimmune disease of the central nervous system (CNS) that leads to myelin damage and neurodegeneration. Stem cell transplantation has long been regarded as a viable treatment option for patients with neurodegenerative disorders. The clinical application of autologous neural progenitors in MS is the culmination of almost a decade of basic research conducted at the MSRCNY, which has found that the injection of these cells may decrease inflammation in the CNS and promote myelin repair and/or neuroprotection.

    The ICMS IRB reviewed the treatment protocols, informed consents and the inclusion/exclusion criteria for the study at its November meeting. The IRB, comprised of medical doctors, researchers and non-scientific community members evaluated the therapeutic approach, the scientific foundation and the medical justification for the use of these cells in the treatment of MS. According to David Audley, Executive Director and CEO of the ICMS, "The main purpose of the IRB is to evaluate the safety of the therapy. After reviewing the study and all the supporting materials, we were convinced that the therapy was not going to put patients at undue risk, and that the treatment itself is the practice of medicine."

    ABOUT THE MSRCNY www.msrcny.org Founded in 2006 by Dr. Saud A. Sadiq, The Multiple Sclerosis Research Center of New York (MSRCNY) is a non-profit research organization solely focused on discovering the cause and cure for multiple sclerosis. MSRCNY helps people with MS by conducting cutting-edge, translational, patient based research to ensure unparalleled care for patients. The close relationship of the research center and the clinical practice (IMSMP) helps to test new treatments for MS and easily moves research discoveries into application to treat symptoms of MS and halt or reverse damage caused by the disease. Patients benefit from the research laboratory by investigation into the cause of MS, disease mechanisms and a devotion to the latest technology to improve MS treatment and care.

    ABOUT THE IMSMP www.imsmp.org The International Multiple Sclerosis Management Practice (IMSMP) is the leader in MS healthcare. It has established a comprehensive level of care for individualized attention to patients' needs and well-being. As the clinical arm of the MSRCNY, the goal of IMSMP is to take bench research and apply it safely to the bedside with extraordinary service and compassion. As an international MS center, patients throughout the United States and from more than 40 countries on 5 continents rely on and visit the IMSMP for care.

    ABOUT THE ICMSThe ICMS is a physician guided international 501(c)(3) nonprofit organization dedicated to patient safety and the protection of the practice of medicine and physician education through the production of global standards for the practice of cell based medicine. The society maintains two websites, www.cellmedicinesociety.org , focused on adult stem cell education and awareness for physicians and researchers and www.stemcellwatch.com , a portal for patient education and information about therapies provided at stem cells clinics around the world.

    Source: Multiple Sclerosis Research Center of New York Copyright (C) 2011 PR Newswire. (22/11/11)

    Athersys to investigate stem cell treatment for MS

    Stem CellsAthersys has entered a partnership with a nonprofit multiple sclerosis group to investigate its adult stem cell technology for the treatment of MS.

    Fast Forward, a nonprofit subsidiary of the National Multiple Sclerosis Society, will commit up to $640,000 to fund animal studies of Athersys’ MultiStem in treating MS, a disease that attacks the central nervous system and can lead to paralysis, according to a statement from Cleveland-based Athersys.

    The goal of the animal studies is to support the submission of an Investigational New Drug application to the U.S. Food and Drug Administration and then begin human trials in patients diagnosed with chronic progressive MS. If the MS project hits unspecified milestones related to development and commercialization, Athersys would remit some payments to Fast Forward.

    Athersys’ MultiStem is an off-the-shelf stem cell treatment derived from the bone marrow of adults or other nonembryonic sources. The technology has shown promise in reducing inflammation, protecting damaged tissue and forming new blood vessels.

    Because research into MultiStem’s application to MS is in such an early stage, it would likely be about 10 years before any treatment would make it onto the market. Lots of expensive development and clinical trial work stands between Athersys and getting a MultiStem MS treatment approved for commercialization.

    “Fast Forward’s partnership with Athersys reflects our commitment to seek out and fund innovative biotechnology companies with products that address critical unmet needs for treating MS that could lead to improved quality of life for people living with this debilitating disease,” said Timothy Coetzee, Fast Forward’s chief research officer.

    MS wreaks havoc when the body’s own immune system begins to attack myelin, a fatty insulating substance that protects and sheaths nerve fibers. Myelin is important because it helps transmit electrical signals from one part of the brain to another.

    When myelin becomes damaged, scar tissue forms and inhibits the body’s ability to transmit nerve signals. That can lead to numbness in the limbs, or more seriously, paralysis and blindness. About 400,000 Americans are affected by MS.

    For a small biotech company like Athersys that’s operating on a shoestring budget and has no products on the market, partnership deals like the one with Fast Forward are key to defraying the high cost of drug development.

    Athersys has entered several similar development partnerships with various companies for the application of MultiStem to different therapeutic areas, including inflammatory bowel disease with Pfizer, heart attack with Angiotech Pharmaceuticals and orthopedics with RTI Biologics.

    Source: Medcity News Copyright 2011 MedCity News.(24/10/11)

    New method isolates best brain stem cells to treat MS

    Areas in red indicate mouse brain cells coated with myelin, a crucial substance lacking in patients with MSThe prospect of doing human clinical trials with stem cells to treat diseases like multiple sclerosis may be growing closer, say scientists at the University at Buffalo and the University at Rochester, who have developed a more precise way to isolate stem cells that will make myelin.

    Myelin is the crucial fatty material that coats neurons and allows them to signal effectively. The inability to make myelin properly is the cause of MS as well as rare, fatal, childhood diseases, such as Krabbe's disease.

    The research, published online and in the October issue of Nature Biotechnology, overcomes an important barrier to the use of stem cells from the brain in treating demyelinating diseases.

    Until now, it has been difficult to separate out the right progenitor cells – the ones that will develop into cells that make myelin, explains Fraser Sim, PhD, first and co-corresponding author on the paper and assistant professor in the Department of Pharmacology and Toxicology in the UB School of Medicine and Biomedical Sciences; he did much of the work while he was a researcher at Rochester.

    "Characterizing and isolating the exact cells to use in stem cell therapy is one key to ultimately having success," said Sim. "You need to have the right cells in hand before you can even think about getting to a clinical trial to treat people. This is a significant step."

    Sim and Rochester graduate student Crystal McClain ran extensive analyses looking at gene activity in different types of stem cells, leading to the conclusion that stem cells carrying a protein known as CD140a on their surface seemed to be most likely to become oligodendrocytes – the type of brain cell that makes myelin.

    The UB and Rochester scientists then injected the cells into the brains of mice that were born without the ability to make myelin. Twelve weeks later, the cells had become oligodendrocytes and had coated more than 40 percent of the brain's neurons with myelin – a four-fold improvement over the team's previous results published in Cell Stem Cell and Nature Medicine.

    "These cells are our best candidates right now for someday helping patients with M.S., or children with fatal hereditary myelin disorders," said Steven Goldman, MD, PhD, co-author, the leader of the team and professor and chair of the Department of Neurology at the University of Rochester Medical Center. "These cells migrate more effectively throughout the brain, and they myelinate other cells more quickly and more efficiently than any other cells assessed thus far. Now we finally have a cell type that we think is safe and effective enough to propose for clinical trials."

    An eventual treatment of a disease like M.S. might involve injecting stem cells to create myelin in the brains of patients.

    "Another approach," says Sim, "might involve using certain medications to turn on these cells already present in the brains of patients and thereby create new myelin. The use of the new techniques described in this work will permit us to better understand how human cells behave in the brain and help us predict which medications may be successful in the treatment of myelin loss."

    The new approach may also be applicable to Krabbe's Disease, Sim says, which also involves the breakdown of myelin. Sim, who came to UB in 2009, is actively collaborating on related work with researchers at the Hunter James Kelly Research Institute, a partnership between UB and the Hunter's Hope Foundation and located in UB's New York State Center of Excellence in Bioinformatics and Life Sciences.

    In addition to Sim, McClain, and Goldman, other authors of the paper include Martha Windream, assistant professor in the Department of Neurology and technical associates Steve Schanz and Tricia Protack, all of the University of Rochester. The work was supported by the National Institute of Neurological Disorders and Stroke, the National Multiple Sclerosis Society, the New York State Stem Cell Research Board, the Adelson Medical Research Foundation and the Mathers Charitable Foundation.

    Source: University Of Buffalo © 2011 UNIVERSITY AT BUFFALO (13/10/11)

    Stem cell breakthrough discovery for multiple sclerosis

    StemcellsResearchers have discovered a way to produce huge amounts of myelinating cells in short periods of time – paving the way for revolutionary treatment in neurodegenerative diseases.

    How we use our senses and the ways that we respond to them is a common part of what makes us human. More specifically, the communication between special nerve cells called neurons in our nervous system is especially important if we expect to sense, think, and move.

    A part of what makes neurons work so efficiently is the protein myelin – a smooth layer of protein that helps speed up nerve impulses between neurons. Losing this myelin causes significant nerve damage; and is the hallmark of debilitating diseases like cerebral palsy and multiple sclerosis.

    But scientists at Case Western Reserve University of School of Medicine have discovered a way to produce copious amounts of myelinating cells in a short period of time using stem cells.

    “The mouse cells that we utilized, which are pluripotent epiblast stem calls, can make any cell type in the body,” Paul Tesar explains, an assistant professor of genetics at Case Western Reserve University and senior author of the study.

    So Tesar’s team set out to transform these stem cells into myelinating cells. In the past, scientists have failed to change these stem cells into cells that will create myelin; resulting only in an unwanted mix of other cell types.

    But Tesar’s team was able to produce more than one trillion myelinating cells in only 10 days using special signaling proteins, growth factors, and thyroid hormone.

    The resulting oligodendrocytes – cells that produce myelin – were tested in cells outside the body and in animal models. Tesar and his fellow colleagues found that these cells restored normal myelin in a matter of days.

    The Case Western researchers believe that this could be replicated in human cells.

    “The ability of these methods to produce functional cells that restore myelin in diseased mice provides a solid framework for the ability to produce analogous human cells for use in the clinic,” said Robert H Miller, vice dean for research at the school of medicine and one author of the paper.

    Perhaps in the future, individuals with demyelinated diseases may be able to treat themselves using their very own cells.

    Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells. Najm et al. Published online: 25 Steptember 2011/ doi.: 10.1038/nmeth.1712

    Source: Examiner.com Copyright © Clarity Digital Group LLC (26/09/11)

    New clinical trial using adult mesenchymal stem cell transplantation for MS

    Stem CellsA team of researchers at three landmark Cleveland institutions have come together to launch a new clinical trial of an experimental treatment for multiple sclerosis (MS). Researchers at the Cleveland Clinic, University Hospitals Seidman Cancer Center, and Case Western Reserve University are collaborating on a ground-breaking study that will test the feasibility and safety of using the body's own stem cells to treat MS.

    In patients with MS, the immune system abnormally attacks the central nervous system, causing damage to the nerve cells and their protective myelin sheath. The body has mechanisms that attempt to repair this damage; however, in MS, the repair cannot keep pace with the ongoing damage.

    The Phase 1 trial involves harvesting a patient's mesenchymal stem cells (MSCs), which are primitive cells in the bone marrow, culturing them in a laboratory, and then injecting the MSCs intravenously back into the patient to see if the procedure is safe, decreases disease activity, and leads to improved repair.

    The research team is headed up by Jeffrey Cohen, MD, of the Cleveland Clinic's Mellen Center for Multiple Sclerosis Treatment and Research, and is funded by a $2.75 million, four-year grant from the United States Department of Defense and a $1 million grant from the National Institutes of Health. Dr. Cohen is Director of the Mellen Center's Experimental Therapeutics Program and Professor of Medicine (Neurology) in the Cleveland Clinic Lerner College of Medicine of the Case Western Reserve University School of Medicine. He has taken a lead role in a large number of MS clinical trials, including a Phase 3 trial that led to the recent approval of the first oral therapy for MS.

    "Currently, there are eight medications approved to treat MS. They slow the disease but none of them reverses it. The hope is that mesenchymal stem cells will lessen ongoing damage caused by MS and promote repair," said Dr. Cohen. "We're taking a cautious approach, carefully monitoring for any unexpected side effects, as we look to see if MSC have the abilities that we anticipate."

    MSCs have a wide range of effects that decrease the activity of immune cells while encouraging tissue repair, both of which may be beneficial in MS. In addition, in numerous laboratory studies, MSCs were able to migrate from the blood into areas of inflammation or injury in the nervous system and reduce damage probably by creating a tissue environment that encourages the body's intrinsic repair processes.

    Study participants will be monitored very closely for six months after they receive the MSC transplantation, including physical exams, blood work, and other testing to determine whether the procedure is safe and well-tolerated. The research team will also monitor their disease status through quantitative neurologic exam, vision testing, advanced MRI, and optical coherence tomography of the retina prior to and for six months after MSC administration to evaluate whether the procedure impacts the activity or severity of each participant's MS. Finally, in collaboration with investigators at the Montreal Neurological Institute, the immunologic effects of MSCs will be comprehensively assessed, both in culture and in the patients.

    Cleveland is one of only a handful of locations in the country where a research endeavor like this could be conducted because it is home to a "dream team" of clinical and research experts with strong collegial relationships; located less than two miles from each other:

    They include:
    Cleveland Clinic's Mellen Center for Multiple Sclerosis Treatment and Research, part of the Neurological Institute;
    University Hospitals (UH) Seidman Cancer Center Coleman Clinical Research Suite;
    Cellular Therapy Laboratory (CTL) based in the Case Western Reserve University School of Medicine National Center for Regenerative Medicine (NCRM), a multi-institutional program comprised of investigators from Cleveland Clinic, Case Western Reserve University, UH Case Medical Center, Athersys, Inc., and the Ohio State University.
    The research process will involve:
    Baseline testing, including general and neurologic exams, vision testing, MRI, and optical coherence tomography, conducted at Cleveland Clinic's Mellen Center.
    Participants have their bone marrow aspirated from their hip in the Coleman Clinical Research Suite at UH Case Medical Center.
    The stem cells will be culture-expanded in the CTL in the NCRM then frozen.
    Participants then have their stem cells infused in the Mellen Center.
    Follow-up monitoring and testing will be done at the Mellen Center.
    Dr. Cohen's study utilizes the CTL based in the Case Western Reserve University School of Medicine NCRM, which is the only academic cleanroom facility for cellular therapy procedures in Northeast Ohio. The role of the CTL is to culture expand or "manufacture" the human MSCs for reinfusion into study subjects.

    This study requires a specialized Class 10,000 cleanroom environment and uniquely qualified personnel because the study subject's marrow cells need to be grown ex vivo (outside of the body) for approximately a month to achieve an adequate number of MSCs. Once the desired dose is obtained, the cells are tested extensively to confirm they are viable and not contaminated to ensure safety, then cryopreserved. At a later date, they are transported to Mellen Center, carefully thawed, and infused intravenously. This type of cell manipulation is performed under the authority of the US Food and Drug Administration and must follow strict procedures, documentation, environmental and equipment monitoring, and quality assurance that is not feasible in a typical research lab.

    The bone marrow harvesting is performed by physicians in the Coleman Clinical Research Suite in the UH Seidman Cancer Center (formerly known as the UH Ireland Cancer Center). UH Seidman Cancer Center is widely regarded as a pioneer in the field of hematopoietic (non-embryonic) stem cell transplantation, particularly in the development of MSCs to treat blood cancers. The first in-human trial of MSCs was published in 1995 by researchers from Case Western Reserve University and UH Seidman Cancer Center. Subsequently, UH Seidman Cancer Center conducted the first-in-humans trial of MSCs in autologous hematopoietic cell (blood/marrow) transplant (2000) and the first-in-humans trial of MSCs in allogeneic hematopoietic cell transplant (2005).

    Arnold Caplan, professor of biology at Case Western Reserve University who was involved in the first in-human trials of MSCs, and Robert Miller, a professor of neurology and associate dean for research at the Case Western Reserve School of Medicine, laid the groundwork for the current clinical trial. They discovered that in mice that have a form of MS, human MSCs promote healing of damage and protect against an autoimmune response. Drs. Caplan and Miller are members of the clinical trial's advisory committee.

    Dr. Stanton Gerson, M.D., director of the UH Seidman Cancer Center and director of the National Center for Regenerative Medicine (NCRM), said, "This trial in MS is one of the most innovative trials of MSCs as it truly investigates both the clinical aspects as well as the science of what these cells do and how they may confer therapeutic benefit to recipients."

    Dr. Gerson also added, "This trial is real joint venture. We have the experience of collecting, expanding, and infusing MSCs. Cleveland Clinic has extensive expertise in MS clinical trials using ultra-sophisticated imaging and other techniques. All three centers (Case Western Reserve, UH Case Medical Center, and Cleveland Clinic) have great basic neurologic science to understand what is happening with the cells and the patients."

    The Phase 1 study, which will take two to three years to complete, will involve 24 patients with relapsing-remitting or progressive MS who have moderate to severe disability. If this trial demonstrates that MSC transplantation is safe, future studies will more definitively assess the efficacy of this therapy in MS. The study has already enrolled 4 patients, and the team expects to begin to report their initial findings over the next 1-2 years.

    More information on the study is available at http://www.clinicaltrials.gov

    Stella's HSCT Blog

    Source: Medical News Today © MediLexicon International Ltd 2004-2011 (27/08/11)

    Doctors begin major stem cell trial for MS patients

    Stem CellsA major clinical trial will investigate whether stem cells can be safely used to treat multiple sclerosis (MS).

    It is hoped eventually to slow, stop or even reverse the damage MS causes to the brain and spinal cord.

    The trial, involving up to 150 patients across Europe, is due to start later this year.

    Dr Paolo Muraro from Imperial College London said: "There is very strong pre-clinical evidence that stem cells might be an effective treatment."

    Researchers will collect stem cells from the bone marrow of patients, grow them in the laboratory and then re-inject them into their blood.

    The stem cells will make their way to the brain where it is hoped that they will repair the damage caused by MS.

    The research has been part-funded by the UK's MS Society, which is concerned about the availability of unproven stem cell treatments.

    In recent years many people living with MS have been attracted to overseas stem cell clinics which claim to cure long-term conditions in exchange for large amounts of money.

    But there is no proven stem cell therapy available for MS anywhere in the world.

    The MS Society hopes these new trials will eventually lead to a proven treatment - and a reduction in the draw of overseas treatments.

    Common condition

    MS is the most common neurological condition to affect young people in the UK.

    Three million people are thought to be affected worldwide and up to 100,000 in the UK.

    The condition is caused by the body's own immune system attacking and damaging a substance called myelin in the brain and nerve cells.

    The myelin damage disrupts messages from the brain to the body which leads to a number of symptoms such as sight loss, bladder and bowel problems, muscle stiffness and eventually physical disability.

    Drugs are available to alleviate the symptoms - but they do not prevent the progression of the condition.

    Experiments in test tubes and laboratory animals suggest stem cells extracted from bone marrow may be able to offer a more effective treatment.

    Their role in the bone marrow is to protect the cells that make blood. But they also seem to protect myelin from attack by the immune system.

    There is also some evidence that these cells might also be able to repair damaged tissue.

    Hold potential

    Dr Doug Brown, of the MS Society, said: "These experiments have confirmed that these stem cells hold that potential - but these need to be confirmed in large scale clinical trials."

    There is some way to go, however, before laboratory promise can be translated into a treatment that can be offered to patients.

    The international team will begin so-called phase two clinical trials in six months' time designed to determine whether the treatment is safe and effective.

    It will take five years to carry out and assess the results of the trials after which large phase three trials may be required.

    But Dr Muraro believes that the stem cell approach has real potential.

    He said: "The great hope is the fact that we are exploiting a biological system that has evolved over millions of years and harnessing it for treatment that takes advantage of the stem cells' flexibility."

    Sir Richard Sykes, chair of the UK Stem Cell Foundation, said Dr Muraro's research was the first of its kind to take place in the UK.

    "Given the high incidence of MS in the UK in comparison to other countries, I am delighted that we have at last progressed stem cell research to this stage, which will bring much-needed hope to so many people affected by this devastating condition."

    The MS Society is also funding two other stem cell studies.

    One, based at Queen Mary Hospital, London will examine how stem cells made from the brains of aborted foetuses can be used to repair nerve damage in people with MS.

    The other, based at the University of Nottingham, will compare stem cells from people with a progressive form of MS to those without the condition to aid the discovery of effective treatments.

    Source: BBC News © British Broadcasting Corporation 2011 (29/07/11)

    MS stem cell trial at Burden Institute gets $1m grant

    Stem CellsDoctors in Bristol are to carry out a trial using stem cells on 80 multiple sclerosis (MS) patients following a $1m (£610k) donation.

    People selected will have their bone marrow harvested which is then filtered before being injected into their blood.

    Trials on a smaller group of people last year found it increased nerve function by up to 20%.

    The research is taking place at the Burden Neurological Institute based at Bristol's Frenchay Hospital.

    MS is a nervous system disorder which affects an estimated 100,000 people in the UK.

    It can lead to a variety of symptoms, including muscle weakness, extreme fatigue, loss of co-ordination and visual and speech difficulties.

    'Encouraging repair'
    As the cells come from the patients' own bodies there are no ethical issues surrounding their use.

    Professor Neil Scolding, who leads the team , has described the donation from the Silverman Family foundation in American as a "godsend".

    He said: "When you inject these cells in to the bloodstream they do find their way into the brain and spinal chord.

    "We know once they get there they are capable of encouraging repair of damage in a variety of ways."

    Half of the group will have the injection immediately and the two groups will be compared after a year.

    The second group will have their treatment a year later as it is thought unethical to deny them the potential benefits.

    One of the patients who had the treatment last May is David Franks.

    Mr Franks had to retire from his job as a children's surgeon early because of his MS.

    He said: "I am not any worse. I may be a bit better.

    "But I am certainly not going down hill as fast as I was before the treatment".

    Source: BBC News © British Broadcasting Corporation 2011 (01/06/11)

    Stem cell transplants may treat aggressive MS

    Stem CellsStem cells have long been used to treat cancer patients, but they are still considered experimental in autoimmune diseases like multiple sclerosis.

    But many believe they offer great hope.

    “It’s the only therapy to date that has been shown to reverse neurologic deficits,” says Richard K. Burt, MD, chief of the division of medicine-immunotherapy for autoimmune diseases at Northwestern University’s Feinberg School of Medicine in Chicago. “But you have to get the right group of patients.”

    In Burt’s study, which was published in The Lancet in 2009, 17 out of 21 patients with relapsing-remitting MS improved after stem cell transplants, and none had gotten worse after an average of three years.

    As a follow-up to that study, Burt and collaborators in Brazil and Sweden are recruiting patients for a study comparing stem cell transplants to Tysabri, a biologic drug, for the treatment of multiple sclerosis.  He is not involved in the current research.

    “You have to do it earlier in the disease, that’s where the excitement is, and that’s why we’re doing the randomized trial,” Burt says.

    Another article, published in the February issue of Multiple Sclerosis Journal, shows that steps taken before the stem cells are transplanted back into the body may have an effect on how well the procedure works.

    Before the stem cells can be reintroduced, patients go through a conditioning process with chemotherapy, either alone or in combination with radiation, in an attempt to wipe out their dysfunctional immune systems. That’s called a high-intensity conditioning regimen.

    But a different kind of conditioning, called intermediate-intensity or ”mini” stem cell transplantation, doesn’t try to kill off all of the errant immune system.

    “There was a tendency for there to be longer progressive-free survival in the studies that used the intermediate-intensity regimens compared to those that used the high-intensity regimens,” says James T. Reston, PhD, MPH, a research analyst in the Evidence-Based Practice Center at the ECRI Institute in Plymouth Meeting, Pa., an independent, nonprofit group that reviews evidence for experimental therapies.

    Source: WebMD © ©2005-2011 WebMD, LLC (22/03/11)

    Stem cells may reverse myelin damage caused by Multiple Sclerosis

    Stem CellsFor people who have multiple sclerosis (MS), loss of the protective layers called myelin sheaths results in damage to the central nervous system. Now researchers have found a mechanism that could help make stem cells repair the damage.

    Repaired myelin sheaths would help multiple sclerosis patients

    Multiple sclerosis is a chronic neurological disorder in which the myelin on nerve fibres in the brain and spinal cord are damaged and destroyed. This damage, called demyelination, interferes with the transmission of signals from the brain through the spinal cord and to locations throughout the body.

    MS is also characterized by inflammation, which can result in permanent loss of function and damage to the cells that produce myelin. As a result, the brain is limited in its ability to repair damaged myelin.

    In new research, which was conducted by scientists from the University of Cambridge and the University of Edinburgh, a mechanism has been found that is not only critical for regenerating myelin sheaths, but may also be utilized to make the brain’s own stem cells more adept at regenerating new myelin.

    The results of the study, which were published in Nature Neuroscience, “could potentially pave the way to find drugs that could help repair damage caused to the important layers that protect nerve cells in the brain,” according to professor Charles ffrench-Constant, of the University of Edinburgh’s MS Society Centre for Multiple Sclerosis Research.

    According to the Multiple Sclerosis Foundation, 350,000 to 500,000 people in the United States have multiple sclerosis, and they are part of the 2.5 million people around the world who live with the disease. Multiple sclerosis is more common among women and whites, and usually is diagnosed between the ages of 20 and 50.There is no cure for the disease, and treatment focuses on alleviating symptoms.

    Study author and Professor Robin Franklin, director of the MS Society’s Cambridge Centre for Myelin Repair at the University of Cambridge, notes that “in this study we have identified a means by which the brain’s own stem cells can be encouraged to undertake this repair [of myelin], opening up the possibility of a new regenerative medicine for this devastating disease.”

    Source: EmaxHealth Copyright eMaxhealth.com 2005-2010 (06/12/10)

    Joint stem cell study to investigate multiple sclerosis

    Stem CellsA $2.2 million project by Victorian and Californian researchers will assess whether stem cell therapies can be used to combat diseases such as Multiple Sclerosis and Type-1 diabetes, and help organ transplant recipients.

    Speaking at AusBiotech 2010 in Melbourne today, Innovation Minister Gavin Jennings said the Brumby Labor Government had contributed $575,505 to the project, the fifth to be funded through the $28 million Victoria–California Stem Cell Alliance which was established in 2008 under the Biotechnology Strategic Development Plan.

    “Millions of people around the world suffer from multiple sclerosis, diabetes or need organ transplants. Innovative autoimmune research like this could be the key to improving their quality of life,” Mr Jennings said.

    “This project is critical to us learning more about how to regulate the immune system in a bid to enhance the potential of stem cell derived tissue transplants as therapies to combat MS and other conditions.”

    “The project highlights the value of collaboration between world-leading centres like Victoria and California in biotechnology and stem cell research. It is yet another demonstration of our commitment to take action to improve the quality of life for millions of people around the world.”

    With MS, the body's immune cells attack the central nervous system, affecting the ability of nerve cells in the brain and spinal cord to communicate with each other. The project will evaluate the use of stem cell approaches to develop alternative treatments for MS.

    Leading neuro-immunologist Professor Claude Bernard of Monash Immunology and Stem Cell Laboratories, internationally renowned for his work in the underpinnings of MS, will lead the research team in Melbourne. Professor Kenneth Weinberg leads the Stanford University team.

    “At the moment the initial triggers that activate Multiple Sclerosis remain unknown, but many studies suggest the body's immune system plays a role in the progression of MS,” Mr Jennings said.

    “Success of the study is crucial to arriving at the goal of safely and successfully using stem cell therapies to treat disease and regenerate tissues.”

    Multiple sclerosis affects approximately 2.5 million people worldwide. In Australia it is estimated that there are around 18,000 people with MS. Approximately $35,500 is spent every year on treatment for an individual with multiple sclerosis.

    The California Institute for Regenerative Medicine is co-funding the project with $1.6 million for the research partners in California.

    Source: The Medical News © Copyright 2010 News-Medical.Net (21/10/10)

    Church supports Multiple Sclerosis stem cell project

    Stem CellsResearch being carried out in Bristol into the medical use of adult stem cells to help multiple sclerosis sufferers is being funded by the Catholic Church.

    The church is opposed to embryonic stem cell research because it involves the destruction of embryos, but it supports the use of adult stem cells, which are found in the bodies of all humans.

    In "an inspiring expression of confidence and optimism", £25,000 has been awarded by Catholic parishioners to Bristol professor Neil Scolding, who is undertaking important ethical stem cell research.

    The University of Bristol Institute of Clinical Neurosciences received the funding for the research at Frenchay Hospital.

    Professor Scolding supports the church in the view that "the taking of stem cells from human embryos is ethically indefensible".

    He said: "We are delighted with this contribution to our bone marrow stem cell research programme relating to multiple sclerosis.

    "Not only is it a substantial help in funding our work, but an inspiring expression of confidence and optimism in what we are doing.

    "We firmly believe bone marrow cells could have a valuable therapeutic impact in MS, and both our clinical trial work and our laboratory research are geared towards exploring, developing and maximising this effect – which we hope in the future will also apply to other neurodegenerative diseases.

    "Our immediate aims are to plan and carry out a further larger clinical trial in MS, again using patients' own bone marrow cells, and in parallel to expand our laboratory studies so as to understand how to optimise the use of these cells."

    Bristol Catholic priest Father Michael McAndrew has supported the grant.

    He said: "These grants are the result of donations given on the annual Day for Life."

    Source: thisisbristol © Northcliffe Media Ltd 2010 (26/07/10)

    Stem-cell treatment gives MS patient his life back

    Stem cellsA new stem cell treatment has saved the life of a young Australian with multiple sclerosis, but MS Australia still warns the procedure is "experimental".

    Ben Leahy, 18, suffers from MS. The first sign something was wrong was when his leg became sore.

    "My legs started going numb, probably from my feet up - one leg feet up and my other leg from the waist down," the Canberra student told The 7.30 Report.

    "It was probably over a week but I thought nothing was wrong. Then in a week it probably got really bad."

    So bad that his family, including his step-father, GP Dr Don Curtotti, rushed Ben to intensive care at Canberra Hospital, fearing a brain tumour.

    For his mother Prue, the diagnosis of multiple sclerosis was the least-worst outcome.

    "I was relieved, believe it or not. I am sorry if it sounds stupid but Don had warned me that he could have had a tumour," she said.

    "I wouldn't have thought MS in a boy because it's extremely rare, and so I was relieved. I just thought, 'I am not going to bury my son in the next six months from bone cancer'."

    However, the family's respite was short-lived.

    MS - a disease that attacks the protective sheath around the nerves in the brain and spinal column - is generally a long-term degenerative process.

    But the MS lesions in Ben's brain were multiplying fast, dangerously pressing on areas that controlled his key bodily functions.

    In a matter of weeks, Ben's body started shutting down.

    Rushed back to Canberra Hospital, consultant neurologist Dr Colin Andrews assessed Ben's cascading physical impairments.

    "The onset was over a matter of days, with weakness in his legs and then it progressed to weakness in his arms," Dr Andrews said.

    "Eventually his limbs were totally paralysed and he couldn't breathe without assistance."

    In medical terms, Ben's MS is known as "rapid onset", but the swiftness with which the disease robbed the teenager of his core functions was shocking.

    Dr Andrew's assessment was blunt: "If he wasn't in intensive care he would have died."

    Ben's life was reduced to mere survival.

    "I couldn't talk or move," Ben recalled. "My eyes were opened but no-one would notice that I was still alive."

    The young man's chances of survival were nil and Dr Andrews decided to attempt a treatment he had only heard about from overseas - an autologous stem cell transplant.

    The experimental procedure had never successfully been performed in Australia and required the co-operation of the neurological department at Canberra Hospital. The answer was no.

    "I remember having to go and say [to Ben's parents], 'I'm sorry, I can't get consensus from my colleagues, so what are we going to do now?'" Dr Andrews said.

    'A step in the dark'

    But the Curtottis had undertaken their own research.

    "We had read about a fellow in Athens who had [this] stem cell procedure done well. I was all for it at this stage, it was all we had," Ms Curtotti said.

    Dr Andrews went back to the hospital and this time haematologist Dr Michael Pidcock said yes.

    "It was a step in the dark, " Dr Pidcock recalled. "We hadn't done something like this before."

    The procedure is akin to rebooting the patient's immune system. The first step was to extract some of Ben's stem cells from his bone marrow.

    "Following some chemotherapy and administration of marrow stimulating drugs, the patient's own bone marrow stem cells are harvested from the bloodstream on a machine during a narrow window of time," Dr Pidcock explained.

    Ben's extracted stem cells were stored in Canberra Hospital's liquid nitrogen tank, waiting for his body to be ready to receive them back.

    For this to happen, Ben was subjected to a second dose of chemotherapy to knock out his immune system and remaining bone marrow cells.

    Within weeks of the treatment, Ben was out of intensive care and walking - something he had not been able to do for more than nine months.

    A year later, MRI scans of Ben's brain revealed almost all the life-threatening lesions had disappeared.

    The result is the best in Dr Andrews's long career.

    "It is the most dramatic change that I've ever seen in someone with MS," he said.

    However, for the Curtottis, the decision to proceed with the radical stem cell treatment was taken against the advice of the respected MS Australia.

    "[They told us] we don't do it in Australia and probably won't for another 10 years because there is just not enough information around," Ms Curtotti said.

    MS Australia's consultant, Professor Bill Carroll, justifies this precaution in the interests of protecting vulnerable patients against false hope.

    "I must say however it still is very experimental," Professor Carroll said.

    "The case of Ben Leahy is terrific for Ben, but may not be translatable to all people with MS."

    For Ben the outcome is straightforward.

    "I've got a life again," he said.

    Source: ABC News © 2010 ABC (18/05/10)

    First coordinated international approach to MS stem cell research

    Stem CellsInternational consensus on the future of stem cell transplantation research for people with MS was published today, paving the way for more coordinated global research efforts and potentially better, and quicker, patient access to stem cell clinical trials.

    The guidelines, developed by an international panel of MS experts with input from MS Societies around the world, spell out hope for the future of MS stem cell research and debunk myths about overseas stem cell clinics claiming to cure the condition. The paper appears in the May 6, 2010 issue of Nature Reviews Neurology.

    The consensus is timely, since small-scale trials of stem cells, such as adult mesenchymal stem cells (from bone marrow and other bodily tissues), are already underway or in planning stages 1 for the treatment of multiple sclerosis.

    A public information booklet on stem cells, "Stem Cell Therapies in MS," produced in partnership by MS Societies from the UK, USA, Italy, France and Australia and the MS International Federation, summarizes the current status of stem cell research in MS and frequently asked questions, and is available to download (.pdf).

    Professor Gianvito Martino from the San Raffaele Scientific Institute in Milan, Italy, and Professor Robin Franklin from the University of Cambridge, UK, are lead authors for the landmark guidelines, which:

    - outline the promise stem cell transplantation has shown in early stage clinical trials and ways they could be used to treat MS in the future;
    - describe the different types of stem cells that might be used to treat different types of MS
    - detail methods of delivering these stem cell therapies into patients;
    - highlight best practice in conducting clinical trials to evaluate the safety and efficacy of stem cell therapies in MS.

    The guidelines are the result of an international stem cell consensus summit held in London in May 2009 which was organized by the MS Society in the UK and USA, and supported by the MS Society of Canada, Italy, France, Australia and the MS International Federation.

    Dr. Patricia O'Looney, vice president biomedical research, National MS Society, USA reported, "This unique collaboration and sharing of information among MS specialists around the world will both speed and enhance the research that will one day lead to effective new treatments for those living with MS."

    Researchers have agreed that stem cells are likely to have a significant role to play in the treatment of MS, but also warn that expectations should be realistic. Professor Gianvito Martino said, "At this stage it is unreasonable to claim that stem cells are a magic cure for MS. It is, however, likely that they will one day play an important role in treating the condition."

    Professor Robin Franklin added, "It is only by working together will we get the answer as to whether stem cell transplants hold promise in the treatment of MS. The guidelines will help the research community get to that answer more quickly than we would by working in isolation."

    Source: Medical News Today © 2010 MediLexicon International Ltd (17/05/10)

    Stem cell transplantation in multiple sclerosis

    Stem CellsStem cell transplantation in multiple sclerosis: current status and future prospects.

    This article provides an overview of the current knowledge relating to the potential use of transplanted stem cells in the treatment of patients with multiple sclerosis (MS).

    Two types of stem cells, CNS-derived neural stem/precursor cells (NPCs) and bone marrow-derived mesenchymal stem cells (MSCs) are considered to provide reproducible and robust therapeutic effects when intravenously or intrathecally injected into both rodents and primates with experimental autoimmune encephalomyelitis.

    Furthermore, preliminary safety data concerning the use of intrathecally injected autologous MSCs in patients with progressive MS are available.

    We discuss how the data gathered to date challenge the narrow view that the therapeutic effects of NPCs and MSCs observed in the treatment of MS are accomplished solely by cell replacement.

    Both types of stem cell, when transplanted systemically, might instead influence disease outcome by releasing a plethora of factors that are immunomodulatory or neuroprotective, thereby directly or indirectly influencing the regenerative properties of intrinsic CNS stem/precursor cells.

    Author of the article, Professor Gianvito Martino said: “At this stage it is unreasonable to claim that stem cells are a magic cure for MS. It is, however, likely that they will one day play an important role in treating the condition.”

    Professor Robin Franklin added: “It is only by working together will we get the answer as to whether stem cell transplants hold promise in the treatment of MS. The guidelines will help the research community get to that answer more quickly than we would by working in isolation.”

    Gianvito Martino, Robin J. M. Franklin, Anne Baron Van Evercooren, Douglas A. Kerr

    Source: Nature Reviews Neurology © 2010 Nature Publishing Group (06/05/10)

    Bone-marrow stem cell study in MS shows promising results

    A groundbreaking trial to test bone marrow stem cell therapy with a small group of patients with multiple sclerosis (MS) has been shown to have possible benefits for the treatment of the disease.

    Bone marrow stem cells have been shown in several experimental studies to have beneficial effects in disease models of MS. The research team, led by Neil Scolding, Burden Professor of Clinical Neurosciences for the University of Bristol and North Bristol NHS Trust, have now completed a small trial in patients with MS to begin translating these findings from the laboratory to the clinic.

    The Bristol team report on this pioneering trial in an article published online in Clinical Pharmacology and Therapeutics. The paper, 'Safety and feasibility of autologous bone marrow cellular therapy in relapsing-progressive multiple sclerosis' was performed at the Institute of Clinical Neurosciences, Frenchay Hospital, Bristol and the Bristol Haematology and Oncology Centre.

    The study explored the safety and feasibility of cell therapy in patients with MS. Participants had a general anaesthetic during which bone marrow was harvested. The marrow cells were filtered and prepared so that they could be injected into the patient's vein later the same day.

    The procedure was well tolerated and the participants were followed up for a year. No serious adverse effects were encountered. The results of clinical scores were consistent with stable disease. The results of neurophysiological tests raised the possibility of benefit.

    Professor Neil Scolding said: "We are encouraged by the results of this early study. The safety data are reassuring and the suggestion of benefit tantalising. A larger study is required to assess the effectiveness of bone marrow cellular therapy in treating MS. We are hopeful that recruitment to this phase 2/3 study may begin towards the end of this year.

    "Research into the underlying mechanisms is ongoing and vital, in order to build on these results. We believe that stem cells mobilised from the marrow to the blood are responsible, and that they help improve disease in several ways, including neuroprotection and immune modulation."

    The aim of the trial was to find out what effects, good or bad, bone marrow stem cells has on patients with MS, and their disability.

    Bone marrow is known to contain stem cells capable of replacing cells in many types of tissues and organs - and so is of great interest to those working to develop new treatments for many diseases, including those affecting the nervous system.

    The study has been funded by the Adrian Wright Bequest, The Patrick Berthoud Charitable Trust, the Silverman Family Foundation, The Myelin Project, the Captain SK Trust and The Burden Trust.

    Source: Eureka! Alert (06/05/10)

    New treatment helps MS patients achieve ‘long-lasting remission’

    Stem cells Ottawa doctors, who claim a new medical technique can cause a “very long-lasting remission,” are giving hope to multiple sclerosis patients.

    “The inflammatory nature of the disease has virtually ceased in everyone who has received this transplant,” said neurologist Dr. Mark Freedman, who led the study with bone marrow transplant specialist Dr. Harold Atkins.

    Freedman said he’s hesitant to say that the transplant of bone marrow stem cells can “cure” multiple sclerosis.

    “I hate to use the C-word ... but we’ve induced a very long-lasting remission,” he said.

    Aaron Prentice, 35, said he has been “blessed” to be part of the study, which investigates the theory that a person’s immune system can be reset.

    Stem cells are harvested from the patient’s blood. Next, the patient’s immune system is destroyed through intense chemotherapy. Then the stem cells are reintroduced with the hope that when the immune system grows back, it will no longer attack the nervous system.

    “Kind of like rebooting a computer,” said the Windsor man.

    Multiple sclerosis causes the body’s own immune system to attack the fatty myelin sheaths that surround the axons that transmit electrical signals between the nerve cells in the brain and spinal cord. This hampers the ability of the cells to communicate, leading to a weakening and wasting of the muscles.

    Freedman and Atkins plan to release the results of the research later this year.

    Prentice was living in British Columbia and working as a plumber when he first started experiencing some of the symptoms of multiple sclerosis: dizziness, loss of balance, difficulty walking, blurred vision.

    He was 24 when he lost sight in one eye, leading to a conclusive diagnosis in 1999.

    “It was definitely a shock,” he said.

    Prentice learned of the stem cell transplant study through his neurologist.

    Prentice said he has experienced no complications, and even his hair — lost during chemotherapy — is growing back. Most importantly, his symptoms have not worsened.

    “The study is aimed to stop the progression more so than repair the damage already done,” Prentice said.

    “Some cases have shown improvement afterwards, and I’m hopeful for that. But, at this point, I’m happy if it does not progress anymore.”

    The treatment was only available in Canada through the Ottawa medical study. Prentice was the last of 24 patients who volunteered as trial subjects.

    Part of the criteria for joining the study — launched in October 2000 — was that the patients have aggressive multiple sclerosis and were likely to become severely disabled.

    The MS Society of Canada, which funded the study, states that the bone marrow transplants have generally been “well tolerated.”

    But officials also warned that “each step of this treatment carries a risk of serious complications. These may be severe enough in a small percentage of patients to be fatal.”

    One trial subject died as a result of liver toxicity, leading to changes in the study’s protocol.

    Source: The Vancouver Sun © Copyright (c) Canwest News Service (04/05/10)

    Could stem cells reverse Multiple Sclerosis?

    Stem CellsBiologist Tom Lane and a team of UCI researchers are leading an effort to determine whether a stem-cell-based treatment can repair neurological damage caused by multiple sclerosis.

    More than eight years ago, Tom Lane helped discover a potential way to prevent multiple sclerosis from affecting the central nervous system. Now he’s leading an effort at UC Irvine to determine whether a stem-cell-based treatment can repair neurological damage caused by the chronic disease.

    Lane, a molecular biology & biochemistry professor, is among 15 U.S. researchers who recently received five-year Collaborative MS Research Center Awards from the National Multiple Sclerosis Society. With the $742,500 in funding, he has assembled a team to investigate the use of cell-replacement therapy to regenerate MS-ravaged nerve tissue.

    In people with MS, immune-system T cells attack myelin, the protective coating of nerves, and eventually the nerve fibers themselves. Symptoms may be mild, such as intermittent numbness in the limbs, or severe, such as paralysis or loss of vision. There is no cure for MS, and current treatments mainly try to limit immune-system response.

    “The promise of cell-replacement strategies to treat MS is significant,” Lane says. “Imagine being able to infuse people with cells that could make new myelin or transform into healthy nerve cells. That’s the focus of our effort.”

    Spinal cord injury research at UCI has already shown the potential of cell-replacement therapy to repair myelin. Neurobiologist Hans Keirstead pioneered a technique to turn human embryonic stem cells into myelin-making oligodendrocyte precursor cells (OPCs) that, he demonstrated, can restore impaired nerve function. These findings form the basis of an upcoming clinical trial involving people with acute spinal cord injury.

    With Keirstead providing the cell lines, the UCI team will explore OPCs’ ability to repair MS-related myelin damage and how the cells could be safely introduced into the body. Researchers and their topics include:

    • Lane studying immune-system messenger cells called chemokines that permit the migration of OPCs to their targeted nerve sites.
    • Dr. George Chandy, physiology & biophysics professor, investigating methods of muting T cell response while OPCs reconstruct myelin.
    • Michael Cahalan, physiology & biophysics professor and chair, developing ways to track and visualize the migration of stem cells and immune cells within the living central nervous system.
    • Dr. Michael Demetriou, associate professor of neurology and director of the comprehensive MS program at UC Irvine Medical Center, examining how enzymes direct T cells and, possibly, OPCs.
    • Dr. Steven Schreiber, neurology professor and interim chair, determining whether niacin can increase the repair capacity of OPCs.

    “With the knowledge acquired from these studies, we believe we’ll lay the foundation for the creation of safe and effective treatments to improve quality of life for people with MS,” Lane says. “UCI has long been a leader in MS research and patient care, and it’s exciting to be part of the significant impact our researchers and clinicians make in this field.”

    Source: Physorg.com © PhysOrg.com 2003-2009 (29/01/10)

    UK Stem Cell Foundation & MS Society stem cell research collaboration

    Stem Cells
    Stem cell research in multiple sclerosis (MS) has been given a much-needed shot in the arm thanks to a partnership between one of the UK's MS Charities and the UK's only charity dedicated to supporting stem cell research.

    The MS Society and the UK Stem Cell Foundation (UKSCF) today (Thursday) formally marked the beginning of the collaboration by announcing a call for research grant applications that can now dip into a dedicated pot of joint-funding up to £1million.

    Dr Doug Brown, Biomedical Research Manager at the MS Society, said the partnership would "pump prime" and speed up stem cell research.

    He added: "We're delighted to announce this partnership that is the first of its kind and look forward to receiving applications for research funding.

    "Stem cells are showing real promise in MS, and the sooner we can take the science from the bench to the bedside, the sooner people with MS will get the answers they so desperately need."

    The potential of stem cells as a treatment for MS has long been the subject of much interest and debate.

    In 2009, the MS Society convened an International Consensus Meeting for stem cell therapies and MS and a number of international experts put forward the view that MS is a condition that could benefit greatly from targeted and increased stem cell research investment and the collaboration is in direct response to that.

    The UK is a recognised global leader in all aspects of stem cell research and in an ideal position to advance stem cell techniques into the clinic for the benefit of billions of people around the globe.

    Progress in this area is being hindered, however, by a critical gap between currently available government and private funding and the countless promising research projects in need of financial assistance.

    Without increasing commitment and funding for research and a push for clinical trials, there are fears these benefits will not be realised.

    "People with MS and the world’s leading researchers have made it clear that more research is needed now," Dr Brown added.

    The MS Society and UKSCF will work together to raise awareness of MS and stem cell research with the aim of attracting high quality research applications.

    Sir Richard Sykes, UKSCF Board of Trustees Chairman, said: "The UK Stem Cell Foundation is delighted to be joining forces with the MS Society to advance the translation of stem cell science towards innovative new therapies for multiple sclerosis."

    Source: UK Stem Cell Foundation & MS Society (14/01/10)

    Multiple Sclerosis - possible autologous stem cell hope

    Stem CellsA U.S. team has achieved encouraging results in the fight against multiple sclerosis (MS) using a new technique of autotransplantation of stem cells extracted from bone marrow of the patient. The results of this clinical trial was conducted on 21 patients in the first phase of the disease have been published in the online version of Lancet Neurology.

    This technique of transplantation of autologous hematopoietic stem cell transplant is the patient's own bone marrow cells. The cells are harvested from bone marrow and the patient receives a cocktail of immunosuppressive anti-rejection drugs. The infusion of these stem cells is then performed intravenously. The latter will somehow "reset" the immune system.

    In this study, 37 months after transplantation, 21 patients have experienced no worsening of their condition, and 17 of them have seen a significant reduction in their handicaps.

    Approximately 100,000 people in the UK suffer from multiple sclerosis whose forms and trends vary greatly from one patient to another. Multiple sclerosis is characterized by destruction of myelin, the protective layer around nerve fibres that carries nerve impulses. Problems with coordination, vision problems, dizziness, motor problems are some of the symptoms of the disease.

    It is an autoimmune disease, ie an immune attack via cell become aggressive, which attack the body itself (in this case myelin). Therefore, researchers try to "reset" the immune system by transplanting hematopoietic stem cells, derived from bone marrow precursors of red blood cells and white blood cells (which include the lymphocytes).

    Source:  Zangani Investor Community © Copyright 2010, Zangani Investor Community™ (07/01/10)

    Stem cells 'reverse' Multiple Sclerosis in Canberra man

    Stem CellsA Canberra man diagnosed with multiple sclerosis (MS) just over 12 months ago appears to be on the road to recovery after being treated with stem cells.

    Ben Leahy was in a wheelchair earlier this year and had suffered partial vision loss in one eye, but has since recovered to the point where he is walking.

    The 20-year-old's remarkable recovery came after he underwent a procedure in which stem cells were harvested from his bone marrow, before chemicals were used to destroy all his existing immune cells.

    Mr Leahy's stem cells were then re-injected.

    ACT neurologist Dr Colin Andrews said the treatment appeared to have reversed the effects of MS which Mr Leahy was diagnosed with in August 2008.

    Dr Andrews said Mr Leahy still had mild weakness in his right leg and some visual loss in one eye, but appeared to be recovering well.

    "At the moment, there's a good chance we may have arrested the disease," he told ABC News.

    The treatment, which carried a risk of death of eight per cent several years ago, was performed in Sydney after Dr Andrews was unable to get the green light from peers in Canberra.

    It has also given hope to other sufferers of the disease.

    Dr Andrews said the treatment offered between a 60 per cent and 80 per cent chance of halting the disease in some patients and a good chance of reversing it in others.

    Almost 20,000 Australians have MS, which affects the central nervous system, prevents nerve impulses from travelling to the brain, spinal cord and eyes.

    While the treatment appears to have reversed the progress of the degenerative disease in Mr Leahy, there is no cure.

    Source: smh.com.au © 2009. Fairfax Digital (15/12/09)

    Stem cell therapy technology possesses promising potential for the future treatment of Multiple Sclerosis

    Stem CellsBrainStorm Cell Therapeutics Inc. a leading developer of adult stem cell technologies and therapeutics, is pleased to announce that the company’s therapeutic approach for treating neurodegenerative diseases, particularly ALS and Parkinson’s disease, was found to have a positive effect in a mouse model of multiple sclerosis (MS).

    In a scientific paper published in the Journal of Molecular Neuroscience, Professors Melamed and Offen’s team from Tel Aviv University studied the effectiveness of human bone marrow derived stem cells induced to differentiate and secrete neurotrophic factors (NTF-SC) as compared to the use of non-differentiated stem cells in a mouse MS model.

    “This study demonstrated that the transplantation of the NTF-SC, based on our novel differentiation technology, resulted in a delay of disease onset and increased animal survival in the mouse MS model to a greater extent than transplantation of the non-differentiated stem cells. It was shown that the NTF-SC modulate the immune system and protect neuronal cells from toxic insults. The positive results in the mouse MS model indicates that our new technology may serve as a possible approach for the treatment of MS,” commented Professor Daniel Offen, Brainstorm’s chief scientific advisor.

    “This study demonstrates that Brainstorm’s approach for differentiating bone marrow stem cells into NTF-SC, may provide an effective strategy not only for the treatment of ALS and Parkinson’s disease but also for the treatment of MS,” said Rami Efrati, CEO of Brainstorm. “As we approach the start of clinical trials for ALS, the Company and its scientific team will continue to study how our technology can be further utilized in the treatment of MS as well as other neurodegenerative diseases.”

    Source: BrainStorm Cell Therapeutics (16/11/09)

    Modifying neural stem cells improves their therapeutic efficacy in MS model

    Stem CellsStem cells isolated from the brain of adult mice (adult neural stem cells [aNSCs]) have shown very modest therapeutic effects in a mouse model of the chronic inflammatory neurodegenerative disease multiple sclerosis.

    But now, Guang-Xian Zhang and colleagues, at Thomas Jefferson University, Philadelphia, have developed an approach to enhance the therapeutic effects of aNSCs in this model of multiple sclerosis.

    The research is reported in the Journal of Clinical Investigation.

    Specifically, the researchers genetically engineered aNSCs to express the anti-inflammatory molecule IL-10 and found that these cells induced more extensive functional and pathological recovery from ongoing disease than did nonengineered aNSCs. Importantly, the IL-10-aNSCs mediated their effects in multiple ways, suppressing immune system attack of nerve cells, promoting nerve cell repair, and promoting production of the nerve cell protective sheath.

    The authors hope these results might increase the chance that aNSC-based therapies might one day be developed for clinical use.

    Journal reference:

    1.Yang et al. Adult neural stem cells expressing IL-10 confer potent immunomodulation and remyelination in experimental autoimmune encephalitis. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI37914

    Source: ScienceDaily © 1995-2009 ScienceDaily LLC (03/11/09)

    Stem cell therapy helps patients with MS, small study shows

    A new stem cell therapy improved the symptoms of early-stage multiple sclerosis (MS) in 80 percent of patients enrolled in a small clinical trial published today in The Lancet Neurology.

    But lead author Richard Burt, chief of immunotherapy for autoimmune diseases at Northwestern University's Feinberg School of Medicine, cautions that the results have yet to be confirmed in large randomised clinical trials. 

    MS is a chronic debilitating neurological disorder that may cause symptoms including numbness of the arms and legs, and, in later stages of the disease paralysis and vision problems. Scientists believe that it's an autoimmune disorder in which the body's immune system – which ordinarily goes after invading germs—attacks healthy tissue. In the case of MS, the patient's immune system destroys myelin sheaths that protect the nerve cells, or neurons, disrupting signals between the brain and the rest of the body.

    Using a method known as autologous non-myeloablative haemopoietic stem cell transplantation, Burt and his colleagues essentially eliminated misbehaving immune cells and replaced them with healthy ones (made from stem cells) in 21 patients (11 women and 10 men) with relapsing-remitting MS, a common form of the disease in which symptoms come and go.

    The way they did this: patients were given drugs that prompted their bone marrow to release immune stem cells (which have the ability to morph into any type of immune cell) into the blood; they then extracted the cells from the blood and gave patients drugs that wiped out their overactive immune systems. The researchers then injected the patients with their stem cells that had been removed earlier; the stem cells quickly divided, giving rise to a fresh batch of normal immune cells in the patients.

    The idea behind the therapy, Burt says, is to "regenerate a new immune system" that recognizes healthy tissue and does not destroy the protein sheaths.
     
    After an average follow up time 37 months, 17 of the patients (80 percent) scored better on a standard test used to gauge their vision, muscle strength, motor coordination, and other aspects of neurological function than they had before the trial. The other four patients did not improve, but they also didn't get any worse, Burt notes.

    The next critical step is to figure out how the stem cell therapy stacks up against existing treatments for MS, such as tysabri and novantrone. These meds slow the disease by blocking or suppressing overactive immune systems, but they do not improve symptoms. Burt says he's currently conducting another clinical trial with 110 MS patients in which he is comparing the safety and effectiveness of the stem cell therapy and MS drugs.

    Source: www.scientificamerican.com 23/07/09

    Stem cell transplant study shows promise for Multiple Sclerosis

    Stem Cells

    U.S. researchers have reversed multiple sclerosis symptoms in early stage patients by using bone marrow stem cell transplants to reset the immune system.

    Some 81 percent of patients in the early phase study showed signs of improvement with the treatment, which used chemotherapy to destroy the immune system, and injections of the patient's bone marrow cells taken beforehand to rebuild it.

    "We just start over with new cells from the stem cells," said Dr. Richard Burt of Northwestern University in Chicago, whose study appears in the journal Lancet Neurology.

    Multiple sclerosis occurs when the immune system mistakenly attacks the myelin sheath protecting nerve cells. It affects 2.5 million people globally and can cause mild illness in some people and permanent disability in others.

    Symptoms may include numbness or weakness in the limbs, loss of vision and an unsteady gait.

    "MS usually occurs in adults," Burt said in a telephone interview. Before they get the disease, their immune systems work well, he said, but something happens to make the immune system attack itself.

    His approach is aimed at turning back the clock to a time before the immune system began attacking itself.

    Burt said the approach -- called autologous non-myeloablative hematopoietic stem-cell transplantation -- is a bit gentler than the therapy used in cancer patients because rather than destroying the entire bone marrow, it attacks just the immune system component of the marrow, making it less toxic.

    Burt and colleagues tried the treatment on 21 patients aged 20 to 53 with relapsing-remitting multiple sclerosis, an earlier stage in the disease in which symptoms come and go.

    Patients in the study were not helped by at least six months of standard treatment with interferon beta.

    After an average follow-up of about three years, 17 patients improved by at least one measure on a disability scale, and the disease stabilized in all patients.

    Patients continued to improve for up to 24 months after the transplant procedure, and then stabilized. Many had improvements in walking, vision, incontinence and limb strength.

    "To date, all therapies for MS have been designed and approved because they slowed the rate of neurological decline. None of them has ever reversed neurological dysfunction, which is what this has done," Burt said.

    Other teams have seen improvements in patients using a more aggressive approach. In one study led by Dr. Mark Freedman of the University of Ottawa last year, 17 MS patients treated with the more aggressive approach were showing signs of remission two years after treatment.

    Burt stressed that the treatment approach needed to be tested in a more scientifically rigorous randomized clinical trial, in which half of the patients get the transplant treatment and the other half get standard treatment.

    That trial is under way.

    Commenting on the study, Helen Yates, MSRC Chief Executive said, “This further piece of research into the use of stem cells with Multiple Sclerosis patients provides another piece of evidence that stem cells could one day provide clear therapies and treatments for MS.  MSRC hopes that further work in this area proves as positive as this piece of research”

    Source: The Vancouver Sun © 2008 - 2009 Canwest Publishing Inc and MSRC (10/06/09)

    Gordon Brown urged to commit millions for multiple sclerosis stem-cell research

    Stem Cells

    Prime Minister Gordon Brown has been urged to guarantee millions of pounds for research into stem-cell therapies for multiple sclerosis.

    The MS society said that without large-scale government support for clinical trials the new hope offered by stem-cell science may be lost.

    It wants to see a specific injection of £3 million to move stem-cell technology from laboratories to hospitals. Four years ago the government announced £50 million for stem-cell science. But since then, the MS Society said, little has been done to promote research into practical stem-cell treatments for conditions such as multiple sclerosis.

    Stem cells are immature cells that can develop along a number of different pathways. Scientists hope some of them may be used to create replacement neurons for brain and nervous system diseases.

    Source: news.scotsman.com All rights reserved ©2009 Johnston Press Digital Publishing (18/05/09)

    Positive results of stem cell transplantation to treat Multiple Sclerosis reported

    Stem Cells

    An article published in the Summer 2009 edition of Multiple Sclerosis Quarterly Report, a joint publication of United Spinal Association and the North American Research Committee on Multiple Sclerosis (NARCOMS), highlights the positive initial results of patients who have improving neurologic function after receiving a stem cell transplant, despite no longer taking any MS medications.

    The results are reported in a National Institutes of Health (NIH)-sponsored study called HALT-MS to confirm whether high-dose immunosuppression followed by autologous stem cell transplantation will prevent MS attacks in patients who are not responding to available treatment options and ultimately protect against the degeneration of nerve fibers.

    The article, written by George H. Kraft, MD, MS, director of the Western MS Center in Seattle, Washington, and colleagues, reveals the promising outcomes of the first three patients entered into the HALT-MS Study, including a 27-year-old woman with an 8-year history of relapsing MS who was treated with five different MS drugs, but continued to have relapses.

    The study involves wiping out the patient's immune system through high-dose chemotherapy or other means, such as radiation, to destroy most blood cells and bone marrow. Blood "stem cells" with the capacity to generate new blood and immune cells are then transplanted into the patient. These stem cells can either be the patient's own or those from a matched donor. Once the cells are transplanted, they repopulate the bone marrow and restart building all the cell types found in the blood, a process called "engraftment". After transplantation, the patient would effectively have a "new" immune system that would not attack nerves in the brain and spinal cord as seen in MS.

    Currently, there are approximately 400 patients with MS worldwide who have been treated with stem cell transplantation. Research demonstrates that patients with highly active forms of relapsing-remitting MS have responded best to treatment.

    The Halt-MS Study is taking place at four centers in the US: The Fred Hutchinson Cancer Research Center/University of Washington Western MS Center; Ohio State University; Baylor College of Medicine; and M.D. Anderson Cancer Center, and is currently open to participants with severe relapsing forms of MS.

    Source: United Spinal Association (08/05/09)

    Stem cells from fat tissue offer hope for Multiple Sclerosis treatment

    Stem Cells

    A preliminary study on the use of stem cells obtained from a patient's own adipose tissue in the treatment of multiple sclerosis (MS) has shown promising results. The three case studies, described in BioMed Central's open access Journal of Translational Medicine, support further clinical evaluation of stromal vascular fraction (SVF) cells in MS and other autoimmune conditions.

    Thomas Ichim, from Medistem Inc., and Dr. Boris Minev, from the Division of Neurosurgery, University of California San Diego, worked with a team of researchers to demonstrate the possible effectiveness of SVF cells in MS treatment. Minev said, "All three patients in our study showed dramatic improvement in their condition after the course of SVF therapy. While obviously no conclusions in terms of therapeutic efficacy can be drawn from these reports, this first clinical use of fat stem cells for treatment of MS supports further investigations into this very simple and easily-implementable treatment methodology".

    MS is an autoimmune condition, in which the body's own defences attack nerve cells, resulting in loss of their fatty myelin sheath. The first symptoms usually occur in young adults, most commonly in women. It is believed that SVF cells, and other stem cells, may be able to treat the condition by limiting the immune reaction and promoting the growth of new myelin. According to Minev, "None of the presently available MS treatments selectively inhibit the immune attack against the nervous system, nor do they stimulate regeneration of previously damaged tissue. We've shown that SVF cells may fill this therapeutic gap".

    Minev and his colleagues provided the SVF treatment to three patients with MS. The first had suffered frequent painful seizures for the previous three years; after treatment he reported that the seizures had stopped completely and that he had seen significant improvements in his cognition and a reduction of spasticity in his arms and legs. The second patient reported improvements in his sense of balance and coordination, as well as an improved energy level and mood. The final patient had been diagnosed with MS in 1993. After SVF treatment in 2008, his gait, balance and coordination improved dramatically over a period of several weeks. According to Minev, "His condition continued to improve over the next few months and he is currently reporting a continuing improvement and ability to jog, run and even bicycle".

    Journal reference:

    Neil H Riordan, Thomas E Ichim, Wei-Ping Min, Hao Wang, Fabio Solano, Fabian Lara, Miguel Alfaro, Jeorge P Rodriguez, Robert J Harman, Amit N Patel, Michael P Murphy and Boris Minev. Non-Expanded Adipose Stromal Vascular Fraction Cell Therapy for Multiple Sclerosis. Journal of Translational Medicine, 2009

    Source: ScienceDaily © 1995-2009 ScienceDaily LLC (24/04/09)

    Genetically modified stem cells treat MS like disease in mice

    White Mouse

    Mice with a human equivalent of multiple sclerosis have been successfully treated using genetically modified stem cells, say a group of Australian researchers.

    The work, led by Dr James Chan of Monash University's Centre of Inflammatory Diseases, may lead to the development of a similar technique to treat autoimmune diseases in humans.

    Autoimmune diseases, such as type 1 diabetes and multiple sclerosis, are caused when immune cells, called T cells, incorrectly identify proteins created by the body as foreign objects, such as bacteria, and attack them.

    To prevent theese rogue T cells from entering the bloodstream, the immune system lures them with 'self-proteins' while they are developing in the thymus. T cells that bind tightly to these self-proteins are destroyed by the body's immune system.

    Some slip through this 'net' and for some people result in auto-immune disease.

    Fully recovered
    Chan and colleagues genetically modified a specific type of stem cell, which produce more self-protein to ensure that dangerous T cells are more effectively removed from the system.

    In the study, which appeared in the Journal of Immunology, mice were inoculated to develop experimental autoimmune encephalomyelitis (EAE), the human equivalent of multiple sclerosis. The genetically modified stem cells were then transplanted into the mice.

    "After the transplantation, the mice are completely resistant to disease," says Chan.

    While initial results are promising, Chan says human clinical trials would not be possible for some time.

    "Before we transplant the stem cells we wipe out the immune system of the mice using high doses irradiation," says Chan.

    He says this level of irradiation would not suitable for humans.

    The team is now looking at ways of overcoming the need for radiation, in order to make the procedure clinically viable.

    Promising
    Dr Carola Vinuesa of the John Curtin School of Medical Research at the Australian National University in Canberra, says the results are "very exciting and potentially very promising."

    But Vinuesa cautions that it is unclear how well the mouse model relates to human disease.

    "The EAE mouse model of multiple sclerosis is not a model in which autoimmune disease develops spontaneously, as occurs with multiple sclerosis in humans," she says.

    She adds there is still a lot we don't know about how healthy T cells know not to attack self-proteins.

    "The mechanism by which they do this is still unclear, but the results [from this study] are spectacular," says Vinuesa.

    Source: ABC Science © 2009 ABC (10/04/09)

    Stem cell inhibition of Multiple Sclerosis by IDO induction

    Stem Cells

    One of the very interesting things is trying to figure out how stem cells mediate their therapeutic effects in conditions such as multiple sclerosis. In general there are three main ways: 1) Differentiation into neurons/oligodendrocytes; 2) Secrete growth factors; and 3) Immune modulation.

    We are going to discuss a publication (Matysiak et al. Stem cells ameliorate EAE via an indoleamine 2,3-dioxygenase (IDO) mechanism. J Neuro Immunol 2008 Jan;193(1-2):12-23) dealing with immune modulation by stem cells in the mouse model of multiple sclerosis. The mouse model is called experimental allergic encephalomyelitis (EAE). In this paper they induced EAE by immunization with proteolipid protein peptide.

    Mice were injected on day 0. Disease severity increases. Mice recieved 2 million intravenous lineage negative stem cell antigen positive. Subsequent to injection disease severity decreased in the treated group. So the question was whether the stem cells were inducing immune modulation.

    To assess immune modulation the authors evaluated recall response and reported that there was suppressed PLP peptide specific recall response in the mice recieving stem cells. HOWEVER, restimulation of the T cells from mice treated with stem cells resulted in increased interferon gamma production. Interferon gamma is actually associated with inflammation, so this data was very interesting.

    The investigators then sought to see if interferon gamma could be inducing expression of indolamine 2,3 deoxygenase (IDO). This enzyme is associated with suppression of T cells by locally "starving" the T cells of tryptophan. Also IDO is associated with protection of the "fetal allograft" from the maternal immune system.

    The investigators performed Western Blot to assess IDO expression in spleens of stem cell treated and control mice. There was increased basal production of IDO, as well as increase expression in splenocytes of stem cell treated mice subsequent to treatment in vitro with interferon gamma. Additionally, the investigators demonstrated that IDO expression was restricted to the dendritic cell compartment by showing that IDO was found only in the CD11c positive fraction.

    Inhibition of IDO activity by treatment of mice with 1-MT lead to abrogation of the therapeutic effects of stem cell on EAE progress.

    This paper suggests that hematopoietic cells actually induce IDO in dendritic cells as a mechanism of immune regulation. There have been numerous animal models, and early clinical descriptions of stem cells having effects in multiple sclerosis. This paper suggests some possible therapeutic mechanisms.

    Source: StemCellPatents.com © 2006 - 2009 StemCellPatents.com (23/02/09)

    Stem Cell transplant 'resets' immune system and reverses early stage Multiple Sclerosis

    Stem cells

    Researchers from Northwestern University's Feinberg School of Medicine appear to have reversed the neurological dysfunction of early-stage multiple sclerosis patients by transplanting their own immune stem cells into their bodies and thereby "resetting" their immune systems.

    The patients in the small phase I/II trial continued to improve for up to 24 months after the transplantation procedure and then stabilized. They experienced improvements in areas in which they had been affected by multiple sclerosis including walking, ataxia, limb strength, vision and incontinence. The study will be published online January 30 and in the March issue of The Lancet Neurology.

    Multiple sclerosis (MS) is an autoimmune disease in which the immune system attacks the central nervous system. In its early stages, the disease is characterized by intermittent neurological symptoms, called relapsing-remitting MS. During this time, the person will either fully or partially recover from the symptoms experienced during the attacks. Common symptoms are visual problems, fatigue, sensory changes, weakness or paralysis of limbs, tremors, lack of coordination, poor balance, bladder or bowel changes and psychological changes.

    Within 10 to 15 years after onset of the disease, most patients with this relapsing-remitting MS progress to a later stage called secondary progressive multiple sclerosis. In this stage, they experience a steady worsening of irreversible neurological damage.

    "This is the first time we have turned the tide on this disease," said principal investigator Richard Burt, M.D. chief of immunotherapy for autoimmune diseases at the Feinberg School. The clinical trial was performed at Northwestern Memorial Hospital where Burt holds the same title.

    The 21 patients in the trial, ages 20 to 53, had relapsing-remitting multiple sclerosis that had not responded to at least six months of treatment with interferon beta. The patients had had MS for an average of five years. After an average follow-up of three years after transplantation, 17 patients (81 percent) improved by at least one point on a disability scale. The disease also stabilized in all patients.

    In the procedure, Burt and colleagues treated patients with chemotherapy to destroy their immune system. They then injected the patients with their own immune stem cells, obtained from the patients' blood before the chemotherapy, to create a new immune system. The procedure is called autologous non-myeloablative haematopoietic stem-cell transplantion.

    "We focus on destroying only the immune component of the bone marrow and then regenerate the immune component, which makes the procedure much safer and less toxic than traditional chemotherapy for cancer," Burt said. After the transplantation, the patient's new lymphocytes or immune cells are self-tolerant and do not attack the immune system.

    "In MS the immune system is attacking your brain," Burt said. "After the procedure, it doesn't do that anymore."

    In previous studies, Burt had transplanted immune stem cells into late-stage MS patients. "It didn't help in the late stages, but when we treat them in the early stage, they get better and continue to get better," he said.

    "What we did is promising and exciting, but we need to prove it in a randomized trial," Burt noted. He has launched a randomized national trial.

    Helen Yates, Chief Executive of the Multiple Sclerosis Resource Centre (MSRC) said:

    "The results of this study are extremely encouraging.  Stem Cell treatment is an area that holds great hope for people with MS and this study provides another piece of the puzzle. That this study seems to show reversal of damage is particularly positive.

    MSRC has been reporting the development of stem cell treatment for a number of years now and we are delighted to see some of the predicted benefits coming to fruition."

    Source: Scientific Blogging © 2009 ION Publications LLC and MSRC (30/01/09)

    Introducing stem cell based Myelin repair therapies in patients with Multiple Sclerosis

    Stem cells

    Professor Neil J. Scolding, FRCP PhD, University of Bristol Institute of Clinical Neurosciences, U.K., provided a report of his studies of bone-marrow derived cells for the treatment of multiple sclerosis.

    About 30 years ago, investigators began to think that cell therapies might be useful to treat loss of myelin caused by multiple sclerosis (MS). The disease has proved more complex, and tissue repair in the brain and spinal cord more challenging than we first thought. Many factors contribute to myelin and nervous tissue damage in MS.

    Cells capable of myelin repair are present in damaged areas but nonetheless do not seem to repair myelin. This might mean that simply adding more myelin-making cells to lesions won’t be enough to help in this disease. Professor Scolding is studying bone marrow derived stem cells. These have a very limited capacity for turning into myelin forming cells. But they seem to stimulate repair processes that are key to tissue regeneration in MS.

    A small safety study of these cells in six patients with chronic MS is nearing completion. The final report will be made when the data analysis is finished. Dr. Scolding has said, “We are grateful indeed to the Myelin Project for our funding, without which this trial would have proved very difficult to complete.”

    Source: The Myelin Project © The Myelin Project (11/12/08)

    Long term outcomes of autologous hematopoietic stem cell transplantation in progressive Multiple Sclerosis

    Stem Cells

    Abstract

    Background

    Progressive multiple sclerosis (MS) is going with continuously disability and unresponsive to high dose steroid and immunomodulation. The autologous hematopoietic stem cell transplantation (ASCT) has been introduced in treatment of the forms of multiple sclerosis.

    Due to hematopoitic stem cell transplantation involved two processes that are conditioning with high dose immunosuppressive agents and stem cell transfusion.

    The short term outcomes (within 2 years after transplantation) do not preclude the immunosuppressant roles of conditionings, therefore the long term clinical outcomes after ASCT were evaluated for patients with progressive MS.

    Methods

    From Nov. 2001 to Jun. 2008, 34 patients with secondary progressive MS were treated with ASCT in our hospital. Of which, 26 patients were followed up more than 2 years till now. The median follow-up time was 40 months (3–83). There were 25 females (73.5%) and 9 males (26.5%). The median age of the patients was 36(20–51) years. Medium duration of disease was 36 months (15–156), and medium attacking interval time was 6.5 months (4–12). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. BEAM, Tiniposide(600 mg/m2), melphalan(140mg/ m2), carmustin (300 mg/m2)and cytosine arabinoside (800 mg/m2), were administered as conditioning regimen.

    Outcomes were evaluated by the expanded disability status scale (EDSS). No maintenance treatment was administered if no disease progression.

    Results

    No deaths occurred following the treatment. All patients were observed into two groups, active-free group and activity group. The former include neurological improvement and neurological stabilization after transplantation. The latter include activity with progression and relapse without progression after improvement.

    Among 34 patients, 27 patients were in active-free group. Of twenty-one patients were with continuous neurological improvement without any active events. Median EDSS scores decreased from 6.0 (4.5–7.5) at transplantation to 2.0 (1.0–5) at last follow-up(p=0.000). Six patients remained neurological stable compared between the time of transplantation and last follow-up. There were 7 patients were in activity group. Of which, five patients had experience of neurological relapse during the follow-up period. However, the EDSS at relapse was lower than pre-transplantation, as well as the interval time between active events was longer than pre-transplantation.

    The low doses steroid relieved the symptoms in clinical. It seems to back to relapse and remission phase. There are two patients experienced neurological deterioration within 7 months after transplantation and need further immnosuppression treatment. The confirmed active-free survival rate was 79.14% and progression-free survival rate was 94.12% at 83 months according to Kaplan and Meier survival curve. Median remission-lasting time reached 63 months (95%CI 52–74). It was a significant difference compared with 7 months (95%CI 6–7) of pre-transplantation (P=0.000).

    We compared disease activity with attacking interval time, disease duration, patient’s age and EDSS of pre-transplantation. There is a relationship between active-free event and attacking interval time, OR=5.454, P=0.01(95% CI: 1.499 to 19.844,) and without relationship with duration of disease (OR=1.009, p=0.758), patient’s age (OR=1.136, P=0.147 and EDSS (OR=1.178, p=0.864) before transplantation.

    Conclusions

    ASCT with conditioning regimen of BEAM were able to improve or stabilize of neurological manifestations in most of progressive MS patients with failure of conventional therapy in long-term. The disease activitivy of post transplantation has a relationship with attacking interval time of pre-transplantation.

    Juan Xu1,*, Tong Wu2, Li Su1,*, Bing Xin Ji3,* and Wu Han Hui3,*

    1 Hematology, xuanwu hosipital, the Capital University of Medical Sciences, Beijing, China, 2 Beijing Daopei Hospital, Beijing, China, 3 Hematology, Xuan Wu Hospital, Capital university of medical science, Beijing

    Source: Blood © 2008 by American Society of Hematology  (08/12/08)

    New Multiple Sclerosis labs to be officially opened at Frenchay Hospital

    Frenchay Hospital

    Best-selling author Jill Mansell will officially open new state-of-the-art Multiple Sclerosis Stem Cell Laboratories at Frenchay Hospital on Wednesday December 3 at 12 noon.

    The new facilities, at the Burden Neurological Institute, have been refurbished and reequipped thanks to a fundraising appeal launched in 2007.

    The appeal, which has raised £250,000, has also seen the transformation of old laboratories at Frenchay into a purpose-built patient centre for people with multiple sclerosis and their carers. The final touches to this building are currently underway with an officially opening soon.

    The Burden laboratories have been up-and-running for a few months and are being used by staff for research into multiple sclerosis. An ongoing research programme into the use of stem cell treatments for MS sufferers and other therapies is now being accelerated through the new centre.

    Jill Mansell, whose books include Thinking of You, Kiss and Good at Games, was an EEG technician at the Burden when it was based at Stoke Park Hospital (now Blackberry Hill). She left in 1995 to pursue her successful literary career.

    Neil Scolding, Professor of Clinical Neurosciences at the University of Bristol and the North Bristol NHS Trust, said: “We are delighted to welcome Jill back to the Burden to officially open our new laboratories which I guess will be very different to ones she worked in back at Stoke Park.

    “This really is a fantastic opportunity and I am grateful to all the individuals and organisations who have donated to our appeal. We are particularly looking forward to the new year and the opening of the patient centre which, combined with these new laboratories, will make the University of Bristol and North Bristol NHS Trust one of the leading forces in the research and treatment of multiple sclerosis.”

    A significant part of the money raised has been used to purchase equipment that can be easily transferred to the new hospital at Southmead when it opens in 2013.

    Source: University of Bristol (02/12/08)

    Intraspinal implant of mesenchymal stem cells may not heal the demyelinated spinal cord in Multiple Sclerosis

    Stem cells and MS

    Multiple sclerosis is a disease caused by the loss of the myelinated sheath surrounding the nerve fibers of the spinal cord. Therapeutic hope for curing multiple sclerosis and other demyelinating diseases has included the possibility that stem cell transplants could help remyelinate the spinal cord. Accordingly, researchers from the University of Cambridge (UK) conducted experiments using animal models to see if the direct implantation of multipotent mesenchymal stem cells (MSCs) (derived from a different rat's adult bone marrow, i.e. allogenic) into the demyelinated rat spinal cord would be therapeutic and remyelinate the damaged area.

    "MSCs are attractive candidates for cell-based therapies because of their ease of isolation, expansion and potential for autologous application," said Dr. David Hunt, of the Centre for Brain Repair at the University of Cambridge. "A number of in vitro and in vivo studies have reported that MSCs have differentiated into neuronal cells and Schwann cells as well as fat cells and bone cells. Our study showed that direct, intralesional injection of undifferentiated MSCs did not lead to remyelination. Once more, we found that the MSCs migrated into areas of normal tissue and were associated with axonal damage."

    Despite the disappointing results of this study, Dr. Hunt feels that further experimentation with directly implanted MSCs is still called for since a variety of other MSC populations, such as autologous cells whereby the donor and recipient are the same organism, have been used in experimental and clinical settings with some degree of success.

    "Our results contrast with previously published reports that demonstrated robust Schwann cell remyelination after bone marrow stromal cell injection," reported Dr. Hunt. "An important difference in results may lie in the distinct methodologies used to culture MSCs."

    Although MSCs may possess neural differentiation capabilities in vitro, their in vivo behaviour is unpredictable, said Dr. Hunt and his co-authors. However, they agree that MSCs should still be considered a promising tool for treating neurological disorders because they have shown pre-clinical efficacy for treating stroke and MS when injected intravenously with the ability to migrate to areas of inflammation and tissue damage and appear to exert a tissue protective effect through a range of mechanisms including immune modulation.

    "This work demonstrates how important the route of administration and the culture conditions are when considering the efficacy and safety of a stem cell therapy," said Dr. Paul Sanberg, Distinguished Professor at University of South Florida Health and coeditor-in-chief of Cell Transplantation.

    Source: Eureka Alert! (13/11/08)

    Autologous stem-cell transplantation showing promise in neurodegenerative disease

    Stem Cells

    Autologous transplantation of bone-marrow–derived mesenchymal stem cells (MSCs) has been performed safely in patients with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) in a phase 1/2 trial.

    This procedure is feasible, presenter Dimitrios Karussis, MD, neurologist-neuroimmunologist said. It’s not science fiction. We have passed from theory and discussion about stem cells to action.

    The results were presented here at the World Congress on Treatment and Research in Multiple Sclerosis: 2008 Joint Meeting of the American, European, and Latin America Committees on Treatment and Research in Multiple Sclerosis (ACTRIMS, ECTRIMS, LACTRIMS).

    Enhancing Regeneration

    We do have good medications to stop inflammation [in neurodegenerative disease], but still we see that disability accumulates over time and irreversible damage occurs to the neurons and axons, Dr. Karussis said. In addition to immunomodulation, we need something that can help or enhance the regeneration mechanisms of the brain.

    Bone-marrow–derived MSCs have strong neurotrophic and immunomodulatory properties, the authors write, and have been shown to be beneficial in several experimental models of neurological diseases, including experimental allergic encephalomyelitis, a model of MS.

    The ability to easily obtain MSCs from the patient, expand them in culture, and reintroduce them as an autologous graft, as well as the lack of risk for malignant transformation, make these cells excellent candidates for cell therapy, they write.

    Dr. Karussis and colleagues conducted a phase 1/2 trial in 19 patients with ALS and 15 with MS. The MS patients had progressive disease with accumulation of disability and had failed prior immunomodulatory therapy.

    Bone-marrow–derived MSCs were collected from the patients, cultured for 2 months, and then reinjected both intravenously and intrathecally. Patients received a mean of 64.4 million cells. After injection, the patients were followed up monthly for up to 25 months.

    Treatment was safe. By far the most common adverse effects were mild fever and headache, which generally started soon after the injection and resolved within 2 to 3 days. Injection-site reactions were mild, and magnetic resonance imaging (MRI) revealed no unexpected pathologies.

    We have passed from theory and discussion about stem cells to action. In the first several weeks after therapy, disease stabilization was observed in patients with ALS and MS. In addition, some patients with MS saw improvements in their disease parameters, with the Expanded Disability Status Scale (EDSS) score dropping from an average of 6.7 at baseline to 5.9 after 6 months.

    This hint of efficacy was a pleasant surprise, said Dr. Karussis. In multiple sclerosis, there were clear cases of good improvement in functioning. It certainly justifies the continuation of this project.

    Cautious Interpretation

    Rhonda Voskuhl, MD, professor in the department of neurology and director of the Multiple Sclerosis Research and Treatment Program at the University of California, Los Angeles, moderated the session in which the data were presented and was asked for some comment on these findings.

    Having an autologous source of stem cells has the advantage of avoiding both graft-vs-host problems and the ethical issues that are associated with stem cells from fetal sources, for example, Dr. Voskuhl said. But that’s assuming there is nothing inherently disease-promoting in your own bone marrow, which could be the case in a genetic disease, she noted, although she acknowledged that some of these problems might be overcome in vitro prior to injection of the cells.

    But while these results are encouraging, Dr. Voskuhl interpreted them with caution. The good news is it didn’t show toxicity, she said. However, she added, It didn’t show any efficacy in my mind. Without a placebo control you really have to interpret that with a lot of caution, she added.

    Dr. Karussis and his team are continuing their work with stem-cell therapy for MS and ALS. The next step, he said, is to develop controlled trials using more injections, more patients, and longer follow-up, ideally in a multicenter setting.

    Source: Online newspaper of professor Yasser Metwally (05/10/08)

    Stem cell patent granted for activating myelin in Multiple Sclerosis

    Stem Cells

    Stem Cell Therapeutics Corp.  has been issued Australian Patent No. 2003250697, entitled "Oligodendrocyte Production from Multipotent Neural Stem Cells".

    This patent covers methods of producing oligodendrocytes from neural stem cells using granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3), or interleukin 5 (IL-5), either in vivo or in cell culture, as well as oligodendrocyte compositions produced by such methods. This is the first patent to issue in this patent family.

    Dr. Alan Moore, President and CEO, commented as follows:
    "This technology adds to the depth of our patent portfolio by expanding the repertoire of pharmaceutical agents we can use to activate neural stem cells, in this case to produce oligodendrocytes. Neurodegenerative demyelinating diseases such as multiple sclerosis are associated with loss of myelin-producing oligodendrocytes. Further, GM-CSF fits into our "repurposing" approach of using old drugs in new indications for expediting entry into the marketplace. Whether we develop this technology in-house or utilize it as an out-licensing opportunity, this patent adds to our arsenal of commercialization opportunities."

    About Stem Cell Therapeutics Corp.

    Stem Cell Therapeutics Corp. is a Canadian public biotechnology company focused on the development and commercialization of drug-based therapies to treat central nervous system diseases. SCT is a leader in the development of therapies that utilize drugs to stimulate a patient's own resident stem cells.

    The Company's programs aim to repair neurological function lost due to disease or injury. The Company's extensive patent portfolio of owned and licensed intellectual property supports the potential expansion into future clinical programs in numerous neurological diseases such as traumatic brain injury and multiple sclerosis.

    Source: Stem Cell Therapeutics Corp (02/10/08)

    Human stem cells help mice in Multiple Sclerosis research

    Stem Cells

    Human embryonic stem cells injected by Hadassah University Medical Center scientists in the brains of mice with an animal model of multiple sclerosis have for the first time halted the progress of the disease.

    The clinical and pathological symptoms of the potentially devastating autoimmune neurological disorder, which include muscle weakness and paralysis, were significantly reduced, the researchers said.

    Prof. Tamir Ben-Hur, chairman of the Ein Kerem hospital's neurology department, and Benjamin Reubinoff, head of the human embryonic stem cell research centre, have been working together on this and other projects for years.

    The researchers said they expect the influence of the stem cell implantation in counteracting the inflammation will in future be integrated with the use of embryonic stem cells to repair and renew the myelin nerve sheathing in the brain. They believe the "encouraging results" will lead to further developments and eventually to clinical trials in humans.

    The CellCure company, a subsidiary of Hadassit (the Hadassah Medical Organization's research and development arm), will promote the application of the research findings. Clinical trials are due to begin in about three years. The research was funded partially by the National Science Foundation and the Morasha Foundation.

    There are some 6,000 MS patients in Israel and many tens of thousands more around the world. Most are diagnosed before the age of 40.

    The lab results were published over the weekend in the on-line Proceedings of the  Library of Science One[US].

    Michal Aharonovich and Dr. Ofira Einstein of Hadassah and Prof. Hans Lesman of the University of Vienna took part in the research.

    Source: The Jerusalem Post © 1995 - 2007 The Jerusalem Post (08/09/08)

    Hope for Multiple Sclerosis sufferers as city scientist nears breakthrough
    An Edinburgh scientist is nearing a breakthrough that will revolutionise the treatment of Multiple Sclerosis and change the lives of generations of future sufferers.

    Edinburgh University's Professor Charles ffrench-Constant, whose work has largely been funded with £2 million from the author JK Rowling, below, is working on a way of using stem cells to halt the deterioration of sufferers.

    He is carrying out tests on mice and rats to try to find a way of using the cells to repair damage to the brain.

    Combined with the earliest possible detection of MS in patients, Prof ffrench-Constant's work offers the best hope of eradicating its devastating effect on patients.

    He recently appeared in a documentary made by journalist and MS sufferer Elizabeth Quigley, who sees his tests as a possible "cure", although sadly for future generations rather than herself.

    Prof ffrench-Constant, head of the Edinburgh University Centre for Translational Research, is reluctant to talk so boldly, but is confident that progress can be made in combating the disease which affects about 10,000 Scots.

    He said: "We need to identify targets – molecules that contribute to the repair process in the brain. We have identified one interesting new candidate and are progressing with that, as well as trying to identify others.

    "Once we have a positive target we have to see if it is present in patients with MS, we can't assume that just because it's worked on rats and mice.

    "The MS Society has a brain bank with lots of tissues from people who have died from MS. If it is present we would run tests to see whether manipulating the target would have the result we hope. Then we would have the long, complicated process of developing the drug."

    This means a treatment being available to patients in the UK is likely to be ten or 15 years away, although, for many people living with a history of MS in their family that will be a comforting thought.

    Where MS comes from and what triggers it remains a mystery, but it is believed to be at least partly hereditary.

    It is sometimes known as the "Scottish disease" as this country has the highest concentration in the world. It can also be found abroad in areas which have a large Scottish community.

    Countries with a similar latitude to Scotland also have high rates of MS, suggesting that temperature or sunlight could be a factor, and childhood illnesses are also common among sufferers who develop MS in later life.

    About 100,000 people in the UK suffer from MS, the result of damage to myelin, which blocks signals from the brain, prohibiting things like movement and speech.

    A drug that could undo that damage remains the stuff of science fiction, but Prof ffrench-Constant believes something that could stop further degeneration is within reach.

    This combined with early detection to ensure sufferers are treated when their health is still relatively good, could seriously limit the effect MS will have on future generations.

    Ms Rowling, whose mother died in 1990 from respiratory problems linked to MS, has said: "It would mean everything to me if I thought that as a result even one person did not have to go through what my mother did."

    Mark Hazelwood, director of MS Society Scotland, said: "The MS Society Scotland was delighted to be able to provide £2 million funding to help establish this important and groundbreaking centre in Edinburgh."

    Source: Edinburgh Evening News ©2008 Johnston Press Digital Publishing (28/07/08)

    Autologous Haematopoietic Stem Cell Transplantation After Immunosuppressive Therapy Effective and Safe in Multiple Sclerosis
    In patients with multiple sclerosis (MS), immunosuppressive therapy followed by autologous haematopoietic stem cell transplantation elicited high response rates and improved quality of life for up to 6 years.

    The results of the study were presented here at the 18th Meeting of the European Neurological Society (ENS) by Tatiana Ionova, MD, PhD, Department of Haematology, Pirogov National Medical Surgical Center, Moscow, Russia.

    During the last decade, high-dose immunosuppressive therapy followed by autologous haematopoietic stem cell transplantation has been used with increasing frequency as a therapeutic option for patients with MS.

    "The aim of the study was to assess the clinical and patient-reported outcomes in patients who underwent early, conventional, and late transplantation," explained Dr. Ionova in a poster session.

    Fifty-six patients with all types of MS ( primary progressive, secondary progressive, progressive relapsing, relapsing remitting) were included. Their mean age was 32.0 years (range 17-51). Median Expanded Disability Status Scale (EDSS) score at baseline was 6.0, the mean follow-up duration 18 months (range 6-84 months).

    Clinical improvement was defined as a decrease in EDSS score of at least 0.5 points on 2 consecutive visits 6 months apart. Disease progression was defined as an increase of at least 0.5 points after 6 months and/or the appearance of new lesions on magnetic resonance imaging (MRI). Stabilisation corresponded to no change in EDSS score.

    Neurological assessments and quality of life assessments were done at baseline, at discharge, every 3 months until 1 year after the transplantation, and every 6 months thereafter. "As multiple sclerosis is considered an incurable disease, quality of life is the overall treatment goal," emphasised Dr. Ionova.

    MRI scans were done at baseline, at 6 months, at 12 months, and at the end of the follow-up.

    "All patients appeared to respond to treatment", reported Dr. Ionova. Improvement was seen in 62.3%, and stabilisation occurred in 37.7% of patients. Progression after improvement occurred in 7.1% and progression after stabilisation in 11.8% of patients.

    There were no deaths during the course of the study.

    Out of 26 patients included in the quality-of-life analysis, 24 exhibited a response and preserved a good quality of life during the follow-up. No unexpected treatment-related adverse events were observed.

    According to Dr. Ionova, immunosuppressive therapy plus autologous haematopoietic stem cell transplantation appears to be a safe and effective therapy for multiple sclerosis, Dr. Ionova concluded.

    The data obtained point to feasibility of early, conventional, and salvage/late transplantation in MS patients, she said.

    [Presentation title: Treatment Outcomes in Multiple Sclerosis Patients After High Dose Immunosuppressive Therapy With Autologous Haematopoietic Stem Cell Transplantation. Abstract P 731]

    Source: Doctors Guides (c) 1995-2008 Doctor's Guide Publishing Limited (12/06/08)

    Bone marrow treatments restore nerves in multiple sclerosis patients
    An experiment that went wrong may provide a new way to treat multiple sclerosis, a Canadian researcher said on Tuesday.

    Patients who got bone marrow stem-cell transplants -- similar to those given to leukemia patients -- have enjoyed a mysterious remission of their disease.

    And Dr. Mark Freedman of the University of Ottawa is not sure why.

    "Not a single patient, and it's almost seven years, has ever had a relapse," Freedman said.

    Multiple sclerosis or MS affects an estimated 1 million people globally. There is no cure.

    It can cause mild illness in some people while causing permanent disability in others. Symptoms may include numbness or weakness in one or more limbs, partial or complete loss of vision, and an unsteady gait.

    Freedman, who specializes in treating MS, wanted to study how the disease unfolds. He set up an experiment in which doctors destroyed the bone marrow and thus the immune systems of MS patients.

    Then stem cells known as hematopoeitic stem cells, blood-forming cells taken from the bone marrow, were transplanted back into the patients. 

    "We weren't looking for improvement," Freedman told a stem cell seminar at the U.S. National Institutes of Health.

    "The actual study was to reboot the immune system."

    Once MS is diagnosed, Freedman said, "you've already missed the boat. We figured we would reboot the immune system and watch the disease evolve. It failed."

    STEM CELL REPAIR

    They had thought that destroying the bone marrow would improve symptoms within a year. After all, MS is believed to be an autoimmune disease, in which immune system cells mistakenly attack the fatty myelin sheath that protects nerve strands.

    Patients lose the ability to move as the thin strands that connect one nerve cell to another wither.

    Instead, improvements began two years after treatment.

    Freedman reported to the seminar about 17 of the patients he has given the transplants to.

    "We have yet to get the disease to restart," he said. Patients are not developing some of the characteristic brain lesions seen in MS. "But we are seeing this repair." 

    MS patients often have hard-to-predict changes in their symptoms and disease course, so Freedman says his team must study the patients longer before they can say precisely what is going on.

    "We are trying to find out what is happening and what could possibly be the source of repair," Freedman said.

    But he has found some hints that may help doctors who treat MS by using drugs to suppress the immune system.

    "Those with a lot of inflammation going on were the most likely to benefit (from the treatment)," he said.

    "We need some degree of inflammation." While inflammation may be the process that destroys myelin, it could be that the body needs some inflammation to make repairs, Freedman said.

    Immune cells secrete compounds known as cytokines. While these are linked with inflammation, they may also direct cells, perhaps even the stem cells, to regenerate.

    The treatment itself is dangerous -- one patient died when the chemicals used to destroy his bone marrow also badly damaged his liver.

    Source: Reuters Canada © Thomson Reuters 2008 (07/05/08)

    Hopes For Future Stem Cell 'Cure' For Multiple Sclerosis Patients
    Stem-cell treatment could be used to help reverse the effects of multiple sclerosis within 15 years, a leading expert on the disease has said.

    Professor Charles ffrench-Constant, the director of a groundbreaking MS research centre in Edinburgh, said the treatment could be used to halt the decline of patients suffering from the debilitating nerve condition.

    In an interview with The Herald newspaper, Prof ffrench-Constant said stem cells could be used to help repair nerve damage caused by MS.

    He said he wanted to find a way to make the body rebuild myelin - the sheath which protects nerve fibres - using stem cells, which have the ability to turn into different types of tissue.

    At present, medicines can only help reduce the inflammation which causes MS.

    Prof ffrench-Constant told The Herald: "My vision for a patient coming into a clinic in 10 or maybe 15 years' time is they will be given a mixture of drugs to prevent the inflammation and to promote repair. That way, MS would no longer be a chronic, disabling disease."

    He added that he wanted to find ways of using stem cells already present in the brain to make new myelin.

    The MS research centre is part of the Scottish Centre for Regenerative Medicine at Edinburgh University.

    It was launched thanks to a major donation from Harry Potter author, JK Rowling, whose mother died from the condition.

    MS affects an estimated 100,000 people in the UK.

    Source: The Press Association © 2008 The Press Association (23/04/08)

    New study may open new doors to Multiple Sclerosis cell-mediated gene therapy
    Chronic inflammation triggers bone marrow-derived blood cells to travel to the brain and fuse with a certain type of neuron up to 100 times more frequently than previously believed, according to a new study from the Stanford University School of Medicine.

    After the fusion, the blood-cell nuclei begin to express previously silent, neuron-specific genes. The surprise finding in mice suggests that the creation of the fused cells, called heterokaryons, may possibly play a role in protecting neurons against damage and may open new doors to cell-mediated gene therapy.

    "This finding was totally unprecedented and unexpected," said senior author Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor and director of the Baxter Laboratory in Genetic Pharmacology. "We're getting hints that this might be biologically important, but we still have a lot to learn." The research, led by Clas Johansson, PhD, a postdoctoral scholar in Blau's laboratory, was published online in Nature Cell Biology on April 20.

    The bone marrow-derived cells are known as blood stem cells, or hematopoietic stem cells. They can give rise to all the blood and immune cells in the body. Although the progeny of these hematopoietic stem cells have previously been shown to fuse with a variety of other cell types in the body, this fusion occurs so infrequently that it had been thought to have little biological significance.

    Purkinje neurons are large cells in a portion of the brain known as the cerebellum, which is involved in balance and motor control. They form junctions between many other neurons, and they do not regenerate. They are the only cell in the brain shown by Blau and others to fuse with these bone marrow-derived cells in mice and humans.

    Previous studies investigating this cell fusion in mice relied on the use of lethal doses of radiation to abolish one mouse's hematopoietic system prior to introducing blood stem cells engineered to express a green fluorescent protein. The new blood stem cells would then entirely repopulate the animal's now-absent hematopoietic system with green-fluorescing cells whose origin could be easily identified. The researchers could then pick out heterokaryons in the brain by looking for green neurons against a neutral background.

    The researchers, in collaboration with scientists at the University of British Columbia in Vancouver, used this technique in the current study to transplant a single hematopoietic stem cell and prove that the heterokaryons in the brain were derived from blood. However, because such high doses of radiation are known to break down the natural barrier that restricts the flow of cells and molecules between the brain and the blood, Blau and her colleagues wondered if this fusion would still occur under less physiologically traumatic conditions.

    They used a technique called parabiosis to introduce blood cells expressing green fluorescent protein into an unmodified animal. In parabiosis, two mice are surgically joined in such a way that they share a circulatory system. One mouse had been engineered to express the green protein in all its cells, and one had not. Because the animals shared a blood supply for several weeks, about half of the blood cells in the unmodified mouse expressed the green protein-enough to enable the researchers to detect fused cells in the brain.

    The researchers found evidence of fusion between blood cells and Purkinje neurons in this radiation-free system 20 to 26 weeks after surgery. In fact, green heterokaryons were identifiable for up to 20 weeks after the mice were separated, when most of the blood cells in the unmodified mouse had been regenerated as non-colored cells.

    But then Johansson saw something surprising. As in previous experiments, most of the mice had very low numbers of fused cells in their cerebellums, but a few had more. Up to 100 times more.

    "Clas noted significantly more heterokaryons than we ever had in the past," said Blau, "from fewer than 10 in an entire animal to several hundred." When the researchers looked more closely, they found that those animals with higher-than-expected numbers of fused cells also had an inflammatory skin condition common to aging laboratory mice called idiopathic ulcerative dermatitis. This type of chronic inflammation affects the entire immune system of the animal and causes a systemwide immune response.

    The researchers confirmed that the remarkable increase in the numbers of fused cells was related to inflammation by using the traditional radiation/bone marrow transplant approach in mice with dermatitis. Finally, they counted the fused cells that formed in a mouse model of multiple sclerosis - an autoimmune disease characterized by inflammation and damage of the central nervous system. Neurologist and multiple sclerosis specialist Lawrence Steinman, MD, professor of neurology and neurological sciences at the medical school, co-authored the research and provided the mouse model for study. Heterokaryons in some of these mice numbered in the thousands.

    Even more intriguing than the inflammation-induced increase in numbers was a cross-species experiment that showed nuclei from rat blood stem cells that had fused to Purkinje cells in mice stop expressing blood cell proteins and begin to express rat neuron-specific gene products. This switch exemplifies a type of genetic reprogramming that has been a source of ongoing debate and great interest in the world of stem cell research. Such reprogramming is critical to the regeneration of functional tissues by stem cells.

    "What we're seeing is that this phenomenon is happening in real life," said Blau, who next plans to study whether such fusions can rescue damaged or dying Purkinje neurons. "We don't know yet if this function is beneficial, but we now know that there are sites where it happens at fairly high frequencies under certain conditions, and that these nuclei can even be reprogrammed."

    Blau's and Steinman's Stanford colleagues on the research include Sawsan Youssef, PhD; Regis Doyonnas, PhD; Kassie Koleckar and Colin Holbrook; as well as the University of British Columbia's Stephane Corbel, PhD, and Fabio Rossi, MD, PhD.

    The research was funded by the Wenner-Gren Foundation (Sweden), the af Jochnick Foundation (Sweden), the National Multiple Sclerosis Society, the National Institutes of Health, the Canadian Institute of Health Research, the McKnight Foundation and the Baxter Foundation.

    Source: Science daily © 1995-2008 ScienceDaily LLC (21/04/08)

    Pluristem's PLX Cells Show A Statistically Significant Advantage In A Pre-Clinical Study In The Multiple Sclerosis Model

    Pluristem Therapeutics Inc. announced today that a preclinical study utilizing the Company's PLacental eXpanded (PLX) cells showed a statistically significant advantage in ameliorating functional deficiencies in a standard Multiple Sclerosis (MS) animal model. PLX cells are mesenchymal stromal cells (MSCs) obtained from the placenta and expanded using Pluristem's proprietary 3D PluriX™ technology.

    Researchers at Pluristem utilized the Experimental Autoimmune Encephalitis (EAE) animal model for the study, the paradigm for MS in humans. After EAE was induced, a number of the animals were given PLX cells intravenously while the remaining served as a control. There was a significant reduction in the EAE score in those animals given PLX cells versus the control group and this beneficial effect was seen throughout the 25-day duration of the study. The EAE score is a measurement of functional outcomes in the EAE-afflicted animal and correlates closely with a histological improvement in EAE-induced lesions. Additionally, the beneficial effects were similar to when Zappia et. al. used MSCs that were non-placental in origin in this EAE animal model1.

    Zami Aberman, Pluristem's President and CEO said: "We are very excited that our PLX cells were able to demonstrate beneficial results that are statistically significant in this standardized model for Multiple Sclerosis. These results, in addition to our previously announced PLX STROKE results, demonstrate that PLX cells may be useful in the treatment of central nervous system (CNS) disorders and potentially help millions of people. Additionally, we believe this experiment demonstrates we can potentially utilize our off-the-shelf, easy to obtain PLX cells and achieve results that are as good as or better than MSCs obtained from other more difficult to find sources."

    1. Zappia et. al. Mesenchymal stem cells ameliorate experimental autoimmune encephalitis inducing T cell anergy. Blood.2005;106: 1755-1761

    Source: Medical News Today © 2008 MediLexicon International Ltd (16/04/08)

    Stem cell transplant helps Multiple Sclerosis patient
    A midnight flight from Ottawa to Vancouver delivered something of a miracle to Jacky and Tom Telder of Surrey, B.C.

    There she was, the Telders' youngest child, Leah, walking towards them in the airport lobby late Monday amidst the disembarking passengers, grinning and waving a greeting.

    "That was amazing. She walked off.

    . . . I mean, there she was, actually walking," said Jacky of the moment.

    Months earlier Leah, 24, had taken a similar flight, in the opposite direction.

    That time, she was among the last to board the plane, hobbling unsteadily on a walker like an old woman.

    The multiple sclerosis that has afflicted her since her teens had, by that point, robbed her of most of her independence, blurred her vision, muddled her thinking and sapped her strength.

    "It was hard to use a knife and fork to even cut my own food," said Leah.

    At its worst, the disease -- a highly unpredictable auto-immune disorder -- had temporarily confined the former ballet dancer to a wheelchair. "Her body just fell apart," said her mother.

    Hope for Leah came last October, when she became only the 17th -- and the youngest -- MS patient in Canada to undergo a stem cell transplant specifically aimed at curbing the progress of the disease.

    Two weeks earlier, she'd checked into the Ottawa Hospital to take part in an experimental medical study, led by Ontario neurologist Dr. Mark Freedman and Dr. Harold Atkins, a bone-marrow transplant specialist. Like the patients before her, Leah underwent heavy doses of chemotherapy -- enough to completely wipe out her immune system and cause her shoulder-length hair to fall out in chunks. Twice, she endured an uncomfortable six-hour procedure during which she was strapped to a chair, unable to even flinch, as a team of specialists carefully siphoned stem cells from her blood.

    "If she moved even a little, alarms would beep," said Jacky of the extremely delicate procedure.

    The stem cells were then sent to a laboratory where they were "cleaned" before being pumped back into her body.

    The theory behind the $4-million study is that pure stem cells will find their way into the bone marrow and build up a new immune system in the patient, free of MS. The trial began in 2001 and is funded by the MS Scientific Research Foundation.

    Qualifying patients are all between the ages of 18 and 50 and have either failed conventional MS drug therapy, or like Leah, been too sick to ever begin conventional treatment. Patients must show a rapid progression of the disease, yet must still have enough strength to walk, at least with a cane.

    Study co-ordinator Marjorie Bowman said early results of the trial -- which aims to treat 24 patients in total -- will be published this summer.

    According to Bowman, one patient died as a result of the chemotherapy (which is so strong, patients have a one in 20 chance of dying). Of the 16 living patients, three have reported some progression of the disease since undergoing treatment, while the remaining 13 have experienced health improvements.

    Leah is lucky enough to be in the latter category. "I haven't felt this good since before I was diagnosed," she said.

    She can walk on her own again and talk without difficulty. She can make a cup of coffee -- something she hasn't been able to do since she was 21.

    And the majority of her vision has been restored.

    Source: The Calgary Herald © The Calgary Herald 2008 (17/03/08)

    Adult stem cells used to treat Multiple Sclerosis
    After Barry Goudy was diagnosed with multiple sclerosis in 1995, he began losing feeling in his left leg, then his vision started to go.

    "You sit and you cry and you wonder why you and then I went back to my neurologist and said tell me how I can fight this," he said.

    Barry enrolled in a clinical trial in 2003. After five days of chemotherapy to destroy his immune system doctors used his own stem cells to rebuild it.

    "I have no symptoms of MS. I do no treatment for MS, I do no shots," he said.

    Researchers at Northwestern University reviewed the outcomes of about 2,500 cases. They found that adult stem cells appear to be putting some patients with autoimmune diseases in remission and are offering new hope to heart attack patients.

    "It's a whole new approach to these diseases. Rather than just surgery or drugs that you can use, a cellular approach that seems in many different studies to be benefiting the patient," said Dr. Richard Burt.

    The transplant appears to be very safe.

    "There's very low risk. Less than 1 percent mortality from the procedure," said Dr. Burt.

    Barry now leads an active lifestyle, and even coaches an ice hockey team.

    "I've had five years of good life. Five years. If I didn't do the transplant I would probably be in a wheelchair today," he said.

    He knows there are no guarantees about how long his remission might last, but he says he's living proof adult stem cell transplants do work.

    Some of the earliest work on adult stem cells and MS was done in Seattle. A study is now underway at the Fred Hutchinson Cancer Research Center.

    Details of the clicnical trial, which is still recruiting can be found here.

    Source: King TV © 2008 KING-TV (27/02/08)

    Stem Cell Sciences in stem cell production deal with US Myelin Repair Foundation
    Stem Cell Sciences (SCS) says it could have access to scalable and sustainable sources of uniform human brain cells for drug testing, boosting its efforts to discover treatments for multiple sclerosis, after entering into a deal with the US-based Myelin Repair Foundation (MRF).

    Under the terms of the agreement, the MRF-supported Human Neural Assay Center, located at Case Western Reserve University in Cleveland, Ohio, will perfect sustainable methods for culturing SCS' human neural stem cells, providing a reliable source for drug testing.

    The development is important because most early-stage drug tests are currently done using animal cells, which results in a high failure rate for drug development because of the differences between animals and humans.

    Historically, access to primary human brain tissue suitable for cell culture has been extremely limited and tissue that was available has been difficult to sustain in culture.

    Through this collaboration, both organisations expect to develop new methods and materials that can be readily used by the entire neuroscience community. SCS has the right to first refusal on commercialising any new products resulting from this collaboration.

    Source: Hemscott Copyright Thomson Financial News Limited 2008.(30/01/08)

    Cell transplant hope for blood diseases and Multiple Sclerosis
    Thousands of patients with ailments such as multiple sclerosis and sickle cell disease have been given new hope that cell transplants could offer a more effective way to treat them.

    An important step towards the goal of transplanting the parent stem cells that give rise to red blood cells to treat genetic blood diseases, such as sickle cell disease, is reported by an American team.

    Using the same method, it should be possible to treat a person with an autoimmune disease, such as multiple sclerosis, in which immune cells attack the person's own body.

    An immune system transplant, much like a liver, kidney or heart transplant, would give the person a different set of white blood cells that might not attack the body, offering an effective treatment.

    Bone marrow transplants are already used to, in effect, transplant stem cells that make healthy white and red blood cells from one person to another but it is necessary to wipe out the old bone marrow first with radiation, which damages other tissue and can cause lasting effects including infertility, brain damage and an increased risk of cancer.

    Now an elegant and more efficient way to achieve the same result, by focusing only on the stem cells of the body's blood and immune system, is reported in the journal Science by researchers at the Stanford University School of Medicine, California.

    The team has found a way to transplant new blood-forming stem cells from a donor into the bone marrow of mice, effectively replacing their immune systems.

    Many aspects of the technique would need to be adapted before it can be tested in humans, said lead author Prof Irving Weissman but, when surmounted, the benefits are potentially huge, he said.

    To avoid the need to wipe out bone marrow, Prof Weissman, Dr Deepta Bhattacharya and Agnieszka Czechowicz found a way to eliminate only the blood-forming stem cells without affecting bone marrow cells or other tissues, using a toxin that only sticks to blood-forming stem cells, effectively destroying the cells, so implanted cells can take hold.

    "It is essentially a surgical strike against the blood-forming stem cells," says Prof Weissman. When the team transplanted new blood-forming stem cells into the mice, those cells took up residence in the bone marrow and established a new blood and immune system.

    In this way, stem cells can be taken from one person who has a good tissue match and these donor cells implanted into a person with autoimmune disease, such as multiple sclerosis, so that the new immune system would likely no longer attack the nerves of the body.

    Likewise, in people with a genetic blood disorder such as sickle cell anaemia, the new blood system would not have the genetic mutation, eliminating the cause of disease.

    First, the researchers have to develop a way to carry out the same kind of surgical strike on human blood forming cells. They also need to do more animal testing to check the effects of the immune system. Although these steps will take time, Prof Weissman says he considered this work to be the beginning of research that could lead to human studies.

    Dr Laura Bell, research communications officer at the MS Society, comments: "Stem cell studies are an important avenue of research which hold promise in terms of treatments for MS. This early stage study is interesting and we look forward to seeing how the work translates into studies in people with MS."

    "For those whose blood stem cells contain a severe genetic defect such as that causing sickle cell anaemia, replacing them with normal stem cells would enable restoration of normal blood," comments Prof Edward Tuddenham of Royal Free Hospital, London.

    "Bone marrow transplantation has been used for sickle cell anaemia with good results in children, but in adults it is difficult to get the new stem cells to take in the face of rejection by the resident stem cells and their progeny- the immune system."

    "This study is clearly interesting and has great potential. It will clearly be needed to see whether these finding in mice can be translated into benefit for patients," adds Prof Lars Fugger of the Medical Research Council Human Immunology Unit and Department of Clinical Neurology, Oxford University.

    Source: The Daily Telegraph © Copyright of Telegraph Media Group Limited 2007 (23/11/07)

    Immune Ablation and Autologous Stem Cell Transplantation for Aggressive Multiple Sclerosis
    Immunoablative therapy plus autologous stem cell transplantation (ASCT) completely abrogates Multiple Sclerosis relapses and MRI events related to ongoing inflammation for up to 5 years, researchers reported here at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

    Mark S. Freedman, MD, Steering Committee Member and Professor of Neurology, University of Ottawa, and Director, Multiple Sclerosis Research Unit, Ottawa Hospital-General Campus, Ottawa, Canada, presented the 5-year interim analysis from a 3-year phase 2 study.

    "If we completely remove the diseased immune system, we should halt ongoing immune-mediated damage, because we would have removed the mistake," Dr. Freedman said during his presentation. Furthermore, the purified stem cells should be capable of restoring a functional immune system, and might even be capable of stimulating repair.

    Therefore, Dr. Freedman and colleagues conducted a study to determine if immunoablative therapy and ASCT induces long-lasting MS progression-free responses in patients with active and progressive disease who have a poor prognosis.

    They enrolled patients aged 18 to 50 years with active MS with relapses or progression and sustained accumulated impairment. Patients had a high risk of progression, an Expanded Disability Status Scale (EDSS) from 3 to 6, and evidence of current disease activity, and had undergone at least 1 year of other standard MS therapy.

    The main steps of the protocol included stem cell mobilization: cyclophosphamide 4.5 g/m2, followed by granulocyte-colony stimulating factor (G-CSF) 10 mcg/kg/day for 10 days; leukophoresis and CD34+ stem cell collection. The immunoablation comprised: busulfan 9.6 mg/kg; cyclophosphamide 200 mg/kg, and rabbit ATG 5 mg/kg; with the ASCT carried out with G-CSF 5 mcg/kg/day.

    Due to patient safety considerations (one early death due to busulfan-induced complications), busulfan dosing was later modified from 1 mg/kg/dose every 6 hours for 16 doses to 0.8 (0.6 in future) mg/kg IV for 16 doses, to avoid first pass effects and to minimize liver toxicity, Dr. Freedman noted.

    Treatment failure was defined according to any two of the following: significant and sustained EDSS progression; at least two relapses at any time; and Gd+-enhancing lesions on any two consecutive MRI. However, the researchers' original definition of treatment success no longer holds due to difficulties in patient enrolment, particularly into the control arm.

    The 25 patients available for evaluation were aged 26 to 41 years, MS duration of 30 to 128 months, had an EDSS score pre-ASCT of 3 to 6.5, and one to five relapses in the previous 2 years.

    To date, no patient has experienced any attacks since undergoing ASCT. Although mild EDSS progression has been seen in four patients (one being a control subject, +1/1.5), a further three patients have shown EDSS improvements (-2 to -4), while in the remainder of subjects EDSS scores remained being stable. Dr. Freedman also indicated that the individual patient EDSS progression or improvement appear to be related to EDSS at baseline (progression only with EDSS 5.5 or greater).

    For MRI lesions, Dr. Freedman said, "We have been without a single new Gd-enhancing or re-enhancing lesion post-transplantation. In fact, not a single new T2 lesion has developed in any patient since [ASCT]."

    Finally, he gave some particular examples of the evidence of specific, but delayed, clinical improvements seen in some of the Kurtzke functional subscores. "This does suggest to us that in the absence of ongoing inflammation, the brain may be capable of some repair, and maybe this had been stimulated by the transplanted autologous bone-marrow-derived stem cells."

    Funding for this study was provided by Bayer Schering Pharma AG.

    Source: Presentation title: Immune Ablation and Autologous Stem Cell Transplantation for Aggressive Multiple Sclerosis: Interim 5-Year Report. Abstract 73 (23/10/07)

    American University of Beirut tests stem-cell therapy on Multiple Sclerosis patients
    Scientists at the American University of Beirut (AUB) began a pioneering clinical trial earlier this month to test bone-marrow stem-cell therapy on up to six individuals suffering from advanced Multiple Sclerosis (MS), a neurological disease with potentially debilitating effects.

    The trial is among the first being carried out in the world, as part of an international task force created about a year ago, following successful animal trials. AUB professor and neuroscientist Bassem Yamout, who is also a member of the European Charcot Foundation Expert Group on the use of human stem cells for treatment of Multiple Sclerosis, is leading the AUB trial which was launched on October 3. AUB assistant dean for research Ali Bazarbachi and his team will be collaborating with Yamout on this experiment.

    "We think this is the future of treatment in neurology," said Yamout. "For the past 100 years, we have been trying to prevent or improve neurological diseases, but for the first time, we hope to repair the damage already done."

    Through their animal trials, scientists have discovered that stem cells could potentially reverse the damage caused by neurological diseases. With the new clinical trials, researchers are now hoping to recreate the same results in human beings. Basically, each adult human body retains, in certain organs, original embryonic cells, known as stem cells, which have the potential to differentiate into any adult cell type.

    In the multiple-sclerosis clinical trial, scientists at AUB extracted stem cells from an MS patient's bone marrow, grew them in the lab for four weeks, then re-injected 100 million of these stem cells in the patient's cerebrospinal fluid at two points: the lower back and neck. Since the cerebrospinal fluid bathes the spinal cord and brain (which constitute the central nervous system), the injected stem cells can reach areas damaged by the disease.

    It is hoped that once those stem cells settle in the damaged parts of the central nervous system, they will differentiate into new neural cells, replacing dysfunctional ones, thus reversing any disability caused by the disease. Moreover, scientists also expect that these new neural cells will also secrete substances that will aid in repair.

    "We are very hopeful about the results and I personally think that this experiment which is among the first in the world in MS patients will open up a whole new avenue of research in the field of MS therapeutics," said Yamout, following the one-hour operation in which the AUB human trial was initiated in a 36-year-old male who has been suffering from multiple sclerosis since 1996 and has been wheelchair-bound since early 2006. "The patient did very well with no complications and was discharged the following day," Yamout added.

    Patients participating in the trial will be monitored over a 12-month period, allowing scientists to detect any improvement.

    If successful, this trial would have tremendous applications in other neurological diseases, such as Alzheimer's, stroke, Parkinson's and physical trauma to the spinal cord. In other words, people like Christopher Reeve, known to many as Superman, would have had the chance to be cured of his complete paralysis following his equestrian accident.

    Up until now, very few MS patients around the world have been injected with stem cells. The AUB team, which helped set up the protocol needed for the human trials, is initiating one of the first scientifically based stem-cell therapeutic trials involving MS patients in the world.

    Source: The Daily Star Copyright © 2007, The Daily Star. (19/10/07)

    Stem cells trial for MS patients
    A new treatment for multiple sclerosis (MS) is being pioneered near Bristol.

    Six patients at Frenchay Hospital are being injected with their own stem cells in the hope that they will repair damage to the brain.

    Approximately 60,000 people in the UK suffer from MS, an incurable disease of the nervous system.

    Prof Neil Scolding, of the Institute of Clinical Neurosciences, said: "We know stem cells are attracted into the brain, into these areas of damage."

    He added that he hoped the stem cells would "help those areas to stop getting worse" and "repair damage".

    'Lot of hope'

    Liz Allison, an MS patient taking part in the trial, said: "I'm hoping there will be some improvement."

    BBC health correspondent Matthew Hill said: "We've already seen stem cells used on cardiac patients but this is the first time a reputable organisation has tried it out on MS patients.

    "There is a lot of hope riding on these trials but it is very early days yet."

    He added that it was likely to be several months before any conclusions could be drawn regarding the treatment.

    Source: BBC News © BBC 2007

    Stem cell trial gets $2M shot in arm
    In response to “unexpected” positive results, a local research facility conducting a bone marrow stem cell transplant therapy trial has been awarded additional funding.

    The Multiple Sclerosis Society of Canada announced Tuesday that the Ottawa Health Research Institute, a University of Ottawa-affiliated arm of the Ottawa Hospital, will receive $2.4 million over five years to continue and further develop the trial begun in October 2000.

    The procedure, which early on resulted in one death and carries potentially serious side effects, involves employing a patient’s bone marrow cells to replace a diseased immune system with a new, purified one.

    A similar procedure has attained positive results in cancer patients, but has rarely been applied to the treatment of autoimmune diseases such as MS, an often-debilitating, chronic condition affecting the brain and spinal cord.

    More than two dozen patients with rapidly progressive disease were selected for the initial stages of the trial; 18 have received the transplant therapy.

    Another transplant recipient died during the procedure four years ago, effectively bringing further treatment to a halt for more than a year. The transplant program resumed in March 2004, after modifications were made to the procedure.

    Most of the patients who have undergone the transplant procedure have seen their condition stabilise or improve, the MS Society reported. Moreover, additional, unexpected improvements to their condition have been witnessed.

    “The hope was that treatment would stabilise progression of the disease, but researchers have found that some patients have experienced improved vision and improved walking ability,” reported Ottawa Health Research Institute spokeswoman Jennifer Paterson.

    “Part of this money will go to finding out what is causing that tissue repair. Additional funds will go to transplants for six more patients.”

    Source: Ottawasun.com Copyright © 2007, Canoe Inc. All rights reserved (18/07/07)

    New Neurons in Old Brains Exhibit Babylike Plasticity
    Study finds a window of adaptability in newly formed brain cells; may lead to stem cell therapies for neurodegenerative disorders.

    Researchers have identified a "critical period" during which new nerve cells in adult brains have the same capacity to learn as those in developing brains. The finding in mice, reported in this week's Neuron, provides the promise of therapies that may one day limit or perhaps even reverse the damage of neurodegenerative diseases such as multiple sclerosis and Parkinson's.

    Scientists first observed neurogenesis—the creation of new neurons in the adult brain—in animal brains in the 1960s but did not find evidence of it in humans until the late 1990s, says senior study author Hongjun Song, an assistant professor of neurology at the Johns Hopkins University School of Medicine in Baltimore.

    Song says he and his colleagues set out to determine whether the young cells differed from older ones—and, if so, how much and at what stage of development. Using a retrovirus that targets dividing, or reproducing, cells, the team tracked new neurons in the hippocampus (a midbrain structure involved with learning and memory) from their births to their deaths. The scientists could determine the behaviour of cells by measuring their electrophysiological activity during different phases. "In young animals, cells are very active, very plastic, and they can change their properties readily," he says. "This whole process [also] happens in the environment of adult circuitry."

    The team found that there is a two-week window, or critical period, about a month after these new cells hatch during which they act like the neurons of a newborn baby. The researchers cued the new cells with a pattern of electrical activation that mimics the sequence that takes place in the brain of a mouse as it learns about a special spot (such as a corner in its cage where it may receive food or a shock). During this time, the cell synapses (connections that allow neurons to communicate with each other) that are artificially stimulated become stronger.

    This strengthening, known as long-term potentiation, results in more efficient information transmission between cells, and is thought to prime them to learn. "For the young cells, it's much easier to be potentiated, but, also, once they are potentiated, the amount of potentiation is much bigger than with brand-new cells," Song says. "What this does is allow [these young cells] to fine-tune their connections."

    "From these data it seems that for high levels of plasticity what matters is the age of the single neuron and not the age of the brain in which the new neuron becomes incorporated," says Tommaso Pizzorusso, a neurobiologist at the Institute of Neuroscience of the National Research Council in Pisa, Italy. "Unfortunately, adult neurogenesis is limited to very specific structures of the brain and, therefore, the remainder of the brain is left with reduced levels of plasticity typical of 'old' cells."

    Song believes that the new findings may open the door to stem cell–based therapies for diseases like multiple sclerosis, Parkinson's and Alzheimer's in which "mature neurons have died and all those fine connections are gone." He says such treatments could involve injecting young nerve cells, in the regions where they are not already continuously being produced, to upgrade flawed existing neural circuitry. "Introducing young neurons," he says, "can make the older circuitry more plastic and adapt to new conditions."

    Source: Scientific American.com © 1996-2007 Scientific American, Inc. All rights reserved. (24/05/07)

    Stem Cell Therapy In Multiple Sclerosis - Now It Is Time To Really Start
    Clinical research with human stem cells to repair brain damage in MS patients should be intensified. Although not unanimously, this was the main conclusion of an international medical scientific conference on MS and stem cell therapy in Italy today(24/11/06), organised by the independent European Charcot Foundation.

    The promising results of the vast number of experiments in animal models, may not always be predictive for results in man. Hence, to learn if stem cell therapy in MS is as effective and safe as suggested, the focus in R&D must shift from the lab to the clinic.

    According to the 300 scientists gathered today, preconditions to this challenging research are:

    • Autologous stem cells should be used (derived from patients' own bone marrow, skin, blood)
    • Pre-clinical research shows that effectivenes and safety profile of treatment with autologous bone marrow cells are relatively positive, virtually no rejection occurs and ethical considerations are limited; .
    • Harvesting, culturing, purification and storage of the human stem cells should be performed in specialised labs under specific GMP-regulations;
    • Procedures of clinical stem cell trials should be standardised and centrally coordinated, as well as reporting and central database management of all stem cell transplanted patients.
    • Ethical issues should be addressed properly, e.g. how to trade-off the cost/benefit ratio, when the benefit is yet unclear at the given scientific status quo and certain risks cannot be ruled out, while the irreversibly ill patient has no other perspectives anymore.

    Some scientists at the conference, pledged for more fundamental research before stem cell treatment in man should start at all. "It is beyond doubt that there is lots of research work to be done on the nature of brain damage and natural repair mechanisms of nerve tissue, on the interaction between immune system and stem cells and on various other aspects in this complex neurobiological arena.

    However, there is growing, although sometimes inconclusive or casuistic evidence of clinical relevant brain-repair and protective properties of transplanted stem cells. Given the urgency of finding a cure for this widespread, disabling disease, most scientists argued that it is justifiable to arrange a rapid onset of well managed trials", concluded Professor O.R. Hommes, Chairman of the European Charcot Foundation.

    "The proof of concept is available. Now it is time to proceed to the clinic. Therefore, we presented today a concept of a groundbreaking phaseI/II clinical trial, to be executed with some 60 severe MS patients in 5 or 6 centers across Europe. The goal is primarily to evaluate safety and feasibility of the stem cell treatment, and secondly to investigate the repair and protective effect in the brain, as can be monitored with MRI on a cellular level, and in reporting of development of the functional abilities of the patient - as the ultimate parameter," stated Hommes.

    The outline of this decisive trial was thoroughly discussed during this scientific meeting.

    European Charcot Foundation
    Hoeveveld 18 a
    6584 GG Molenhoek (Nijmegen area)
    The Netherlands
    http://www.charcot-ms.eu 

    Source: Medical News today © 2006 MediLexicon International Ltd (24/11/06)

    Study: Bone Marrow Stem Cells May be Successful in Treating Parkinson's and MS
    The results of a study published in the April issue of Stem Cells and Development suggest that human stem cells derived from bone marrow are predisposed to develop into a variety of nerve cell types, supporting the promise of developing stem cell-based therapies to treat neurodegenerative disorders such as Parkinson's disease and multiple sclerosis.

    Stem Cells and Development, a peer-reviewed journal published by Mary Ann Liebert, Inc., carries the paper, entitled "Human Mesenchymal Stem Cells Express Neural Genes, Suggesting a Neural Predisposition." (online here http://www.liebertpub.com/scd)

    The surprising results lend a new perspective to stem cell differentiation and suggest that multipotential stem cells may express a wide variety of genes at low levels and that stem cells achieve their remarkable plasticity by downregulating the expression of many of these background genes.

    While many scientists believed stem cells were the most primitive cells, the study suggests otherwise. In an accompanying editorial, journal Editor-in-Chief, Denis English, Ph.D., Professor of Neurosurgery and Director of Cell Biology at the Center of Excellence for Aging and Brain Repair Research at the University of South Florida College of Medicine in Tampa, writes, "contrary to our current thinking, stem cells are in no sense primitive cells. In fact, stem cells may well be the most advanced cells the organism produces."

    The authors of the report, Netta Blondheim, Yossef Levy, Tali Ben-Zur, Alex Burshtein, Tirza Cherlow, et al., from the Felsenstein Medical Research Center and Department of Neurology at Rabin Medical Center, the Sackler School of Medicine of Tel Aviv University, and Laniado Hospital in Israel, propose this new view of adult stem cell plasticity based on their findings that bone marrow-derived mesenchymal stem cells grown in the laboratory express an extensive assortment of neural genes, genes linked to the neuro-dopaminergic system, and transcription factors that control genes having neural significance.

    They conclude that these MSCs are predisposed to differentiate into neuronal cells given the proper conditions. When transplanted into the central nervous system, they will develop into a variety of functional neural cell types, making them a potent resource for cell-based therapy.

    Source: LiteSiteNews.com (c) Copyright: LifeSiteNews.com (03/05/06)

    Adult stem cell research advances
    A laboratory rat unable to use its right front paw because of a spinal cord injury struggles to walk across a rope, loses its footing and falls.

    Then a rat that had the same injury scurries across the rope without a problem, just weeks after an injection containing adult stem cells from a human nose that were transformed into nerve cells.

    The rats are part of a line of research at the University of Louisville that could lead to treatments for spinal cord injuries, multiple sclerosis, Parkinson's disease and other nerve disorders.

    The rat's improvement after the injection is the second major discovery in the past few months at UofL that promises progress without using embryonic stem cells.

    In December, a research team at the James Graham Brown Cancer Center announced it had transformed stem cells from adult mice into brain, heart, nerve and pancreatic cells.

    The nasal stem-cell research - published most recently last week in the journal Stem Cells - involves using certain chemicals to direct the cells to become neurons, which send and receive messages between the nervous system and other parts of the body.

    "It amazes me still that we can take cells out of a human nose" and help an injured rat recover", said Fred Roisen, a neuroscientist who led the team. "I'm very optimistic."

    Experts said the research is unique.

    "This one has gone a lot further than the others," said Scott Whittemore, who is scientific director of UofL's Kentucky Spinal Cord Injury Research Center but is not on Roisen's research team. "This is a major step forward."

    Robert Miller, a professor of neuroscience at Case Western University in Cleveland, called the research "quite exciting." He said many studies have involved trying to make existing cells reconnect instead of introducing new neurons that promote recovery.

    The UofL researchers said clinical studies in humans could be anywhere from three to 10 years off, and any treatments wouldn't become widely available until after that. But some people who could benefit said they are hopeful.

    "This looks very promising," said Pam Kober, a 46-year-old Louisville resident with multiple sclerosis.

    Kober found out she had MS in 1999 after having headaches and numbness in her arms. Over the years, the illness has left her unable to drive at night, handle more than one household chore at a time or hold a full-time job.

    "Maybe in my lifetime they'll find something that will help," she said.

    The cells the team used came from the tissue that allows people to smell. Called the olfactory neurosensory epithelium, the tissue was taken from adults undergoing elective sinus surgery who volunteered for an endoscopic biopsy. The procedure doesn't harm the sense of smell.

    Researchers then used compounds to coax the cells into becoming neurons that attached to muscle tissue in the lab. The newly created cells can also produce myelin, a protective coating that insulates the nervous system.

    Source: Cincinatti Enquirer Copyright © 1995-2006 (16/03/06)

    Woman with MS shows remarkable progress in stem cell trial
    A Kanata woman has surpassed all expectations after risking her life to take part in a medical experiment for multiple sclerosis.

    Jennifer Molson

    Jennifer Molson

    In 1996 at the age of 21, Jennifer Molson woke up with a tingling in her fingers that spread to her arms. Within a few months, she could hardly move her left side.

    Molson was diagnosed with multiple sclerosis, an autoimmune disease in which the body's immune system attacks itself, causing damage to the spinal cord, nerves and brain.

    Molson has the most common form of MS, the relapsing remitting variety, said Dr. Mark Freedman, a neurologist in Ottawa.

    She eventually needed to use a cane and leg brace and was headed for life in a wheelchair. Freedman asked her to become involved in a medical study with a big hitch.

    "We could offer her a chance at stopping her disease, but at the same there, there was a risk that she may die," said Freedman.

    Over several months in 2002, doctors harvested stem cells from Molson's blood, removed all traces of MS, and then gave her high does of chemotherapy to wipe out her immune system.

    Then the stem cells were transplanted back to her.

    For the first two years, Molson recovered slowly. She planned her wedding and walked down the aisle wearing a wig, but no leg braces.

    The young woman who couldn't tie her shoelaces is now able to go for walks and take care of household chores.

    "I can get in the car and go to work," said Molson. "I can't believe I'm the same person."

    None of the other 11 participants in the study has gotten worse, but Molson has shown the most improvement so far.

    Doctors can't explain why, but the experiment may answer some important questions about MS, said Dr. Jock Murray, past director of the MS clinic at Dalhousie University in Halifax.

    "The idea that you might be able to stop the disease by a process like this one is extremely hopeful," Murray said.

    Molson thinks she is cured but doctors aren't ready to declare it, saying no one knows how long the effects will last.

    Source: cbc.ca © CBC 2006 (16/03/06)

    Stem Cell Therapy International Reports Successful Treatment of Multiple Sclerosis Patient With Stem Cell Transplantation Therapy
    Patient Describes 'Dramatic' Improvement in Video Clip Posted on Company Web Site

    TAMPA, FL--Feb 27, 2006 -- Stem Cell Therapy International, Inc, a leading company in the field of research and development of stem cell transplantation (SCT) therapy and regenerative medicine, reported today the successful results of a case of stem cell transplantation performed last November on a 42-year-old man, who was diagnosed with progressive multiple sclerosis (MS) three years ago.

    Samuel Bonnar, a shop owner in Newtownabbey, Ireland, was experiencing increasing debilitation including difficulty speaking and the effects of poor circulation. He needed crutches to walk and was able to climb stairs only by lifting his left leg with his arm with each step. He had received traditional treatment for MS at two hospitals in Ireland with little to no effect.

    Calvin Cao, CEO of Stem Cell Therapy International (SCTI), said Mr. Bonnar sought alternative treatment for his condition, first learning about stem cell transplantation therapy in the United Kingdom from the non-profit newsletter, "Different Strokes," that detailed the positive treatment of Belfast native Ian McBride, who had suffered a stroke and was successfully treated with stem cell transplantation at the SCTI affiliated medical facility in 2005.

    Calvin Cao said SCTI arranged for Mr. Bonnar to be treated with injections of a stem cell biological solution at the SCTI affiliate medical facility in Kiev, Ukraine on November 27th, 2005. "The positive results of the therapy were remarkable and almost instant," Mr. Cao reported. "Within a few days, Mr. Bonnar's speech and mobility were vastly improved and after two weeks he had regained the ability to climb a full set of stairs without having to lift his left leg with his hand. Numbness in the fingertips of both hands subsided and occurs now only occasionally."

    In a correspondence with SCTI in mid-December, Mr. Bonnar recounted the results: "After the treatment, my speech improved dramatically. It is almost back to the way it was. Other people have commented on the dramatic difference. The doctors at the hospital said it would take two-to-three months to see the full effect of the stem cell transplantation therapy. It has now been 2 1/2 weeks since the treatment and already there is noticeable improvement."

    SCTI has posted a video clip on its web site made in Kiev that shows Sam Bonnar describing his condition both before and after the treatment. To view the video clip, go to: http://www.scticorp.com/sam.cfm.

    Calvin Cao said Mr. Bonar's progress will be monitored over the next six months. There is no follow-up treatment planned at this time. He said that Dr. Weinwen Deng, Ph.D., an expert in stem cell therapy from Tulane University and a member of the SCTI Medical and Scientific Advisory Board, has been asked to prepare a scientific abstract on the case and submit it to an appropriate scientific journal for publication.

    "Sam Bonnar's improvement, along with Ian McBride's, provides increasing evidence of the efficacy of stem cell transplantation therapy and, we believe, will encourage stem cell researchers worldwide to promote widespread acceptance of stem cell therapy worldwide," Mr. Cao said.

    He said, "The stem cell therapy procedure Mr. Bonnar received at the clinic is based on the use of the stem cell biological solution, which is part of the exclusive license agreement SCTI has for the use of 26 patents related to stem cell technology from the Institute of Cell Therapy (ICT). Mr. Bonnar's is another successful case we have treated using our stem cell biological solution and the results have exceeded our expectations."

    With the enactment of Proposition 71 in California in November 2004, a fund of $3 Billion was created to fund stem cell research. Since then four other states, New Jersey, Connecticut, Illinois and Wisconsin, have allocated funds for stem cell research. For additional information about SCTI and its stem cell treatment procedures, you can visit their website at:  http://www.scticorp.com.

    About Stem Cell Therapy International

    Stem Cell Therapy International, Inc. is engaged in the field of research and development of regenerative medicine. SCTI manufactures allo stem cell biological solutions that are currently being used in the treatment of patients suffering from degenerative disorders of the human body such as Alzheimer's, Parkinson's Disease, ALS, leukemia, muscular dystrophy, multiple sclerosis, arthritis, spinal cord injuries, brain injury, stroke, heart disease, liver and retinal disease, diabetes as well as certain types of cancer. The Company has established agreements with highly specialized, professional medical treatment facilities around the world in locations where stem cell transplantation therapy is approved by the appropriate local government agencies. SCTI intends to provide these biological solutions containing stem cell products in the United States to universities, institutes and privately funded laboratory facilities for research purposes and clinical trials. Its products, which are available now, include various allo stem cell biological solutions containing (human stem cells), low-molecular proteins and human growth factor hormones.

    Source: Stem Cell Therapy International, Inc.(27/02/06)

    BrainStorm Files Patent Application for Stem Cell Procedure With Potential for Multiple Sclerosis Therapy

    NEW YORK and TEL AVIV, Israel, Jan. 26, 2006 -- BrainStorm Cell Therapeutics, the developer of NurOwn(tm) bone marrow derived stem cell therapeutic products for the treatment of neurodegenerative diseases, announced today that a patent application has been filed with the U.S. Patent and Trademark Office for a new procedure to derive oligodendrocyte-like cells. The invention involves inducing oligodendrocyte-like cells using the company's proprietary bone marrow derived human mesenchymal stem cell technology.

    The patent application was filed by the technology transfer company of Tel Aviv University, Ramot, on the basis of research funded by Brainstorm. Worldwide rights to the development and commercialization of the new technology are exclusively licensed to BrainStorm.

    "Developing the capability to derive oligodendrocyte-like cells is a major step forward because of the important role that oligodendrocyte cells are believed to have in restoring cell function in patients suffering from Multiple Sclerosis and other demyelinating diseases,'' said Yoram Drucker, Principal Executive Officer of BrainStorm.

    "Now that we have demonstrated that mesenchymal stem cells can be induced to differentiate in vitro to oligodendrocyte lineage and form functional cells, our next goal will be to test the oligodendrocyte-like cells in animal models of Multiple Sclerosis,'' said Dr. Daniel Offen, BrainStorm's Chief Scientist.

    Brainstorm's success in deriving olgodendrocyte-like cells follows several other major technological achievements made by the company during the past year using the company's proprietary bone marrow derived stem cell technology.

    In other studies, Brainstorm successfully used bone marrow stem cells to produce dopaminergic-like cells shown to be capable of dopamine secretion and to benefit animal models of Parkinson's disease.

    Brainstorm also used its bone marrow stem cell technology to produce astrocyte-like cells with the capacity of producing glial derived neurotrophic factor (GDNF), the most potent neurotrophic factor known for dopaminergic neurons. Transplanted dopamine- and GDNF producing-cells, acting on their own or in combination, hold great promise for replacement and preservation of neurons in Parkinson's and other neurodegenerative diseases.

    About BrainStorm Cell Therapeutics Inc.

    BrainStorm Cell Therapeutics Inc. is an emerging company developing neural-like stem cell therapeutic products, NurOwn(tm), based on autologous bone marrow derived stromal cells, for treatment of neurodegenerative diseases. NurOwn(tm) patent-pending technology is based on discoveries made by the team of prominent neurologist, Prof. Eldad Melamed, Head of Neurology at Rabin Medical Center, and expert cell biologist Dr. Daniel Offen, at the Felsenstein Medical Research Center of Tel-Aviv University, enabling the differentiation of bone marrow derived stem cells into functional neurons and astrocytes, as demonstrated in animal models. The company holds rights to develop and commercialize the technology through an exclusive, worldwide licensing agreement with Ramot at Tel Aviv University Ltd., the technology transfer company of Tel Aviv University. The company's initial focus is on developing treatments for Parkinson's Disease.

    About Stem Cell Therapy

    Stem cells are non-specialized cells with a remarkable potential for both self-renewal and differentiation into cell types with a specialized function, such as muscle, blood or brain cells. Stem cells may be sourced from fetal or embryonic tissue or from adult tissue reservoirs such as bone marrow. Use of embryonic stem cells, has become the center of significant ethical and moral debate. In contrast, use of adult stem cells does not face the same moral or legal controversy. Stem cell therapy aims to ``cure'' disease by replacing the 'diseased' cells with 'healthy' cells derived from stem cells. This approach has the potential to revolutionize medicine and, if successful, the implied commercial opportunities are great. Currently, both embryonic stem cells (ESC) and adult stem cells (ASC) are being explored as the potential basis for multiple cell therapy products.

    About Multiple Sclerosis

    Multiple Sclerosis (MS) is a chronic disabling autoimmune neurological disorder targeting the white and gray matter of the central nervous system. The autoimmune attack includes auto-reactive lymphocytes and local inflammatory response that causes demyelination and oligodendrocyte death followed by accumulating axonal damage and axonal loss. In the Western World, the number of prevalent cases of MS totals about 700,000. At present, there is no cure for MS. Available treatments comprise disease-modifying immunosuppressants that have a market of $2.1 billion. The development of a restorative cell therapy would dramatically change the market dynamics.

    Source: BrainStorm Cell Therapeutics(26/01/06)

    BACKGROUND: Certain stem cell transplantation procedures might slow down inflammatory pathology in multiple sclerosis (MS).

    AIMS: To halt disease progression in aggressive MS by a bone marrow transplantation (BMT) protocol aimed at maximum T cell suppression.

    METHODS: Autologous BMT was performed in 14 patients with rapid secondary progressive MS (median EDSS score at baseline, 6; median disease duration, five years). To accomplish rigorous T cell ablation, a strong conditioning protocol was chosen-cyclophosphamide, total body irradiation, and antithymocyte globulin. To minimise the possibility of reinfusing mature T cells in the graft, bone marrow, not peripheral blood, was used as the CD34+ stem cell source.

    RESULTS: Median follow up was 36 months (range, 7-36). Post-transplant haemopoietic recovery was successful in all patients. Early toxicity included Epstein-Barr virus related post-transplantation lymphoproliferative disorder. Longterm effects were development of antithyroid antibodies (three) and myelodysplastic syndrome (one). One patient died of progressive disease five years after transplantation. Treatment failure, defined by EDSS increase sustained for six months or more, was seen in nine patients and stabilisation or improvement in five. Other clinical parameters generally showed the same outcome. No gadolinium enhanced lesions were seen on post-treatment magnetic resonance imaging, in either cerebral or spinal cord scans. However, cerebrospinal fluid oligoclonal bands remained positive in most cases.

    CONCLUSIONS: This strong immunosuppressive regimen did not prevent clinical progression in patients with aggressive secondary MS. The lack of efficacy, together with some serious side effects, does not favour the use of similar rigorous T cell depleting protocols in the future.

    Samijn JP, Te Boekhorst PA, Mondria T, van Doorn PA, Flach HZ, van der Meche FG, Cornelissen J, Hop WC, Lowenberg B, Hintzen RQ

    Department of Neurology, MS Centre ErasErasmus MC, Postbox 2040, 3000 CA Rotterdam, The Netherlands.

    Source: J Neurol Neurosurg Psychiatry 2006 Jan;77(1):46-50.(18/01/06)

    MULTIPLE SCLEROSIS sufferer Tiger Tim Stevens has rejected the chance to travel to Holland for controversial stem cell treatment costing £12,000.

    The 52-year-old Radio Clyde DJ has decided against going to Amsterdam for the treatment that an Inverness woman claims has given her "hope of a normal life".

    Amanda Bryson, 19, has regained the use of her legs after the treatment, which involved injections of stem cells taken from newborn babies' umbilical cords. The treatment is not available in Britain.

    She says the experience has changed her life, but Tiger, despite being in a wheelchair because of the muscle-wasting disease, says he will not take a chance on the injections.

    Tiger, who lives in Hogganfield in Glasgow's east end, said: "It all looked wonderful and I have believed for years that stem cell treatment could be the answer for conditions such as MS.

    "I was all set to have a go and several friends assured me they could raise the money to send me to Amsterdam.

    "However, when I saw the girl who had treatment on television I was disappointed in her mobility. She did not look as if she could walk very well.

    "Then I listened to a TV report with GMTV's Dr Hilary Jones, who warned against the treatment.

    "He said it had not been endorsed by the British Medical Association and the Americans have not sanctioned it either. From that point, I decided to do some more research."

    Tiger studied several reports on the treatment and after reading up he was unsure about the process.

    He said: "I am told there could be some horrendous side-effects, so I will wait a few months and then look again at Amanda Bryson's condition. Believe me, I would love it to work......"

    For the full story please click on the link above. (18/01/06)

    by Jeremy O'Connell
    A multidisciplinary team of UW-Madison researchers recently received a five-year, $3.4 million grant to develop techniques for using stem cells to repair nerve damage in victims of diseases like Multiple Sclerosis, and to improve imaging technology to view the lesions and repairs at the cellular level.

    The grant was part of $30 million slated for research on nervous-system repair and protection as part of a new campaign called Promise 2010.

    MS debilitates the human body like a civil war ravages a country. The immune and nervous systems engage in a fierce battle that invariably leaves the nervous system permanently damaged. Although the rapidly advancing field of MS research has seen five medications approved in just 10 years, these drugs only slow the disease. Doctors are still helpless to cure MS or repair the neurological damage it causes.

    UW-Madison researchers hope to change that.

    “It’s the largest grant we have ever received, and the largest [the National MS Society] has ever given out,” said team leader Ian Duncan, a UW-Madison School of Veterinary Medicine professor. “We wrote a competitive and very compelling proposal for research that could lead to clinical applications.”

    The proposed research employs experts from 10 independent disciplines in addressing the issue of nerve damage in the 2.5 million people MS affects worldwide. (18/01/06)

    © Multiple Sclerosis Resource Centre

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