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Intraspinal implant of mesenchymal stem cells may not heal the demyelinated spinal cord in Multiple Sclerosis
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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) |
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Autologous stem-cell transplantation showing promise in neurodegenerative disease
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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) |
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Stem cell patent granted for activating myelin in Multiple Sclerosis
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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)
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Human stem cells help mice in Multiple Sclerosis research
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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) |
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Hope for Multiple Sclerosis sufferers as city scientist nears breakthrough
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| 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 85,000 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) |
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Autologous Haematopoietic Stem Cell Transplantation After Immunosuppressive Therapy Effective and Safe in Multiple Sclerosis
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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) |
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Bone marrow treatments restore nerves in multiple sclerosis patients
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| 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) |
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Hopes For Future Stem Cell 'Cure' For Multiple Sclerosis Patients
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| 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 85,000 people in the UK. Source: The Press Association © 2008 The Press Association (23/04/08) |
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New study may open new doors to Multiple Sclerosis cell-mediated gene therapy
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| 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) |
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Pluristem's PLX Cells Show A Statistically Significant Advantage In A Pre-Clinical Study In The Multiple Sclerosis Model
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| 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) |
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Stem cell transplant helps Multiple Sclerosis patient
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| 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) |
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Adult stem cells used to treat Multiple Sclerosis
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| 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) |
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Stem Cell Sciences in stem cell production deal with US Myelin Repair Foundation
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| 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) |
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Cell transplant hope for blood diseases and Multiple Sclerosis
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| 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) |
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Immune Ablation and Autologous Stem Cell Transplantation for Aggressive Multiple Sclerosis
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| 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) |
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American University of Beirut tests stem-cell therapy on Multiple Sclerosis patients
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| 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) |
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Stem cells trial for MS patients
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| 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 |
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Stem cell trial gets $2M shot in arm
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| 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) |
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New Neurons in Old Brains Exhibit Babylike Plasticity
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| 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) |
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Stem Cell Therapy In Multiple Sclerosis - Now It Is Time To Really Start
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| 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) |
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Study: Bone Marrow Stem Cells May be Successful in Treating Parkinson's and MS
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| 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) |
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Adult stem cell research advances
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| 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) |
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Woman with MS shows remarkable progress in stem cell trial
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| A Kanata woman has surpassed all expectations after risking her life to take part in a medical experiment for multiple sclerosis. | 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) |
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Stem Cell Therapy International Reports Successful Treatment of Multiple Sclerosis Patient With Stem Cell Transplantation Therapy
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| 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) |
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BrainStorm Files Patent Application for Stem Cell Procedure With Potential for Multiple Sclerosis Therapy
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| 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) |
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Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis.
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| 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)
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I'm not going to Holland for MS treatment ... it just sounds too risky
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| 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) |
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Repairing Nerves, receiving grants
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| 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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