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)

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)

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)

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)

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)

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)

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.

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)

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)

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)

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 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 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 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)

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)

[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)

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)

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)

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 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)

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)

"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)

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)

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)

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)

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)

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

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)

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)

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: Me