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Stem cells

Stem Cells

 

 

 

 

 

 

 

Stem cells reverse multiple sclerosis in small study(21/01/15)

A therapy that uses patients' own primitive blood cells may be able to reverse some of the effects of multiple sclerosis, a preliminary study suggests.

The findings, published Tuesday in the Journal of the American Medical Association, had experts cautiously optimistic.

But they also stressed that the study was small -- with around 150 patients -- and the benefits were limited to people who were in the earlier courses of multiple sclerosis (MS).

"This is certainly a positive development," said Bruce Bebo, the executive vice president of research for the National Multiple Sclerosis Society.

There are numerous so-called "disease-modifying" drugs available to treat MS -- a disease in which the immune system mistakenly attacks the protective sheath (called myelin) around fibres in the brain and spine, according to the society. Depending on where the damage is, symptoms include muscle weakness, numbness, vision problems and difficulty with balance and coordination.

But while those drugs can slow the progression of MS, they can't reverse disability, said Dr. Richard Burt, the lead researcher on the new study and chief of immunotherapy and autoimmune diseases at Northwestern University's Feinberg School of Medicine in Chicago.

His team tested a new approach: essentially, "rebooting" the immune system with patients' own blood-forming stem cells -- primitive cells that mature into immune-system fighters.

The researchers removed and stored stem cells from MS patients' blood, then used relatively low-dose chemotherapy drugs to -- as Burt described it -- "turn down" the patients' immune-system activity.

From there, the stem cells were infused back into patients' blood.

Just over 80 people were followed for two years after they had the procedure, according to the study. Half saw their score on a standard MS disability scale fall by one point or more, according to Burt's team. Of 36 patients who were followed for four years, nearly two-thirds saw that much of an improvement.

Bebo said a one-point change on that scale -- called the Expanded Disability Status Scale -- is meaningful. "It would definitely improve patients' quality of life," he noted.

What's more, of the patients followed for four years, 80 percent remained free of a symptom flare-up.

There are caveats, though. One is that the therapy was only effective for patients with relapsing-remitting MS -- where symptoms flare up, then improve or disappear for a period of time. It was not helpful for the 27 patients with secondary-progressive MS, or those who'd had any form of MS for more than 10 years. Secondary-progressive MS occurs when the disease progresses more steadily and people no longer go through waves of symptoms and recovery.

Between 250,000 and 350,000 Americans have MS, according to the National Institutes of Health (NIH). Most are initially diagnosed with the relapsing-remitting form. Eventually, relapsing-remitting MS transitions to the secondary-progressive form.

It makes sense that stem cell therapy would be effective only in the relapsing-remitting stage, according to Bebo. That's the phase where the immune system is actively attacking the myelin.

Burt agreed, noting that once people are in the secondary-progressive stage, the damage to nerves is done.

A big question is what will the long-range effects will be, according to an editorial published with the study.

MS usually arises between the ages of 20 and 40, according to the NIH. Since disabilities can take decades to develop, the ultimate benefits -- and risks -- of stem cell therapy remain unknown, writes Dr. Stephen Hauser, a neurologist at the University of California, San Francisco.

It's also unclear, Hauser writes, whether the therapy is really "resetting" the immune system.

Bebo agreed. "In this report," he said, "there's no data to show whether that's happening."

What's needed now, Bebo said, are controlled trials where patients are randomly assigned to receive stem cell therapy.

Burt agreed, and said that's what his team is doing: A clinical trial is underway at several medical centers, looking at patients with relapsing-remitting MS whose symptoms have failed to improve after at least six months on standard medications. They're being randomly assigned to either stem cell therapy or further drug therapy.

If stem cell therapy does prove effective, it's hard to say exactly how it will fit in with standard MS care, according to Bebo.

On one hand, the regimen is fairly intensive and expensive. "But in theory," Bebo said, "it would only have to be done once, and never again."

The disease-modifying drugs for MS -- such as beta interferons (Avonex, Rebif, Betaferon), glatirimer (Copaxone) and natalizumab (Tysabri) -- can cost thousands per month, according to the background information in the study.

Comparatively, stem cell therapy, at around $125,000, could prove very cost-effective, according to Burt.

For now, stem cell therapy is available only in clinical trials, or on a "compassionate use" basis for some patients who don't qualify for a trial, Burt said.

If it's eventually approved as an MS therapy, Burt said he foresees stem cells as a "second-line" therapy for patients who do not fare well on a disease-modifying drug.

Source: NEWSMAXHEALTH.COM © 2015 Newsmax Media, Inc (21/01/15)

Report of MS stem cell trial brings hope(05/01/15)

Three years after a small number of patients with multiple sclerosis (MS) were treated with high-dose immunosuppressive therapy (HDIT) and then transplanted with their own hematopoietic stem cells, most of the patients sustained remission of active relapsing-remitting MS (RRMS) and had improvements in neurological function, according to a study published online by JAMA Neurology.

MS is a degenerative disease and most patients with RRMS who received disease-modifying therapies experience breakthrough disease. Autologous (using a patient's own cells) hematopoietic cell transplant (HCT) has been studied in MS with the goal of removing disease-causing immune cells and resetting the immune system, according to the study background.

The Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) study examines the effectiveness of early intervention with HDIT/HCT for patients with RRMS and breakthrough disease. The article by Richard A. Nash, M.D., of the Colorado Blood Cancer Institute at Presbyterian/St. Luke's Medical Center, Denver, and coauthors reports on the safety, efficacy and sustainability of MS disease stabilisation though three years after the procedures. Patients were evaluated through five years.

Study results indicate that of the 24 patients who received HDIT/HCT, the overall rate of event-free survival was 78.4 percent at three years, which was defined as survival without death or disease from a loss of neurologic function, clinical relapse or new lesions observed on imaging. Progression-free survival and clinical relapse-free survival were 90.9 percent and 86.3 percent, respectively, at three years. The authors note that adverse events were consistent with the expected toxic effect of HDIT/HCT and that no acute treatment-related neurologic adverse events were seen. Improvements in neurologic disability, quality-of-life and functional scores also were noted.

"In the present study, HDIT/HCT induced remission of MS disease activity up to three years in most participants. It may therefore represent a potential therapeutic option for patients with MS in whom conventional immunotherapy fails, as well as for other severe immune-mediated diseases of the central nervous system. Most early toxic effects were hematologic and gastrointestinal and were expected and reversible. Longer follow-up is needed to determine the durability of the response," the authors conclude.

In a related editorial, M. Mateo Paz Soldán, M.D., Ph.D., of the University of Utah, Salt Lake City, and Brian G. Weinshenker, M.D., of the Mayo Clinic, Rochester, Minn., write: "This study and another phase 2 single-arm study leave little doubt that high-dose immunotherapy is able to substantially suppress inflammatory disease activity in patients with MS who have active disease in the short term. There is some evidence for long-term suppression of MS. Lessons have been learned about how treatment-related morbidity and mortality may be reduced. However, deaths have occurred, even in small studies, and aggressive regimens have resulted in lymphomas associated with Epstein-Barr virus."

"Nash et al show evidence of prolonged depletion of memory CD4+ cells, depletion of CD4+-dominant T-cell receptor clones and evidence of 'immune reset'; however, clinical or radiologic evidence of relapse trumps immunologic evidence of immune reset, and this study raises concern that those end points have not been adequately achieved. The jury is still out regarding the appropriateness and indication of HCT for MS," the authors conclude.

Source: Medical Xpress © Medical Xpress 2011-2015, Science X network (05/01/15)

Could mouse fat stem cells help study transplantation in Multiple Sclerosis(23/12/14)

Researchers in Spain have found that specific fat stem cells from mice could be excellent tools for studying transplantation of stem cells in autoimmune diseases, such as multiple sclerosis (MS). The work was published in the December 12th issue of the journal, Stem Cell Research & Therapy.

The type of cell is called a “mesenchymal stem cell” or MSC for short. They are found in adults in the bone marrow, but can also be found in other regions like the umbilical cord or regular blood in the circulatory system, as well as the fallopian tubes and lungs.

Scientists are avidly studying these cells for the possible treatment of autoimmune diseases like MS because of their ability to change into almost any cell type. They eventually would like to see whether these cells can be used to treat disease in humans. According to the study authors, “The ultimate goal in MSCs research is to treat human patients at the clinic with their own MSCs, since autologous transplantation provides two main theoretical advantages: a minimisation of the risk of transmission of infectious diseases and an increased efficiency in the absence of rejection by the patient’s immune system.”

If people could use their own MSCs to treat disease, rejection of the cells due to immune responses would be brought to a minimum.

With this idea in mind, researchers decided to test whether cells taken from the fat of mice (adipose tissue) would have the qualities needed for MSCs. This was not just any mouse, but a specific type of mouse called the SJL/JCrl mouse strain, which has been studied in research on retinal degeneration and also in genetically-modified mice (transgenic). This animal was compared to the more commonly-studied C57BL/6 mouse strain.

The scientists, led by Carmen Marin-Bañasco of the Instituto de Biomedicina de Málaga, examined how the stem cells from the SJL/JCrl mouse grow, how quickly they develop, what shapes they take on, and different markers on the surface of the cells that could tell them what type of cell they turn into. In the most critical experiment, the scientists tried transplanting mice with the stem cells that had a mouse version of relapsing-remitting multiple sclerosis, known as experimental autoimmune encephalomielitis (RR-EAE).

Based on their experiments, these particular fat cells had the shape, growth rate, and other cell characteristics that are classic for a potential MSC. Transplanting the fat stem cells helped the mice with the experimental form of MS, by reducing markers of inflammation in the spinal cord and brain and making the nervous system tissue take on a less-diseased appearance.

The authors concluded that the fat cells in this type of mouse might be useful for testing transplantation in animals, before researchers conduct similar studies in humans. Similar types of cells would then need to be studied in greater detail in humans, but could eventually be useful for “their application as promising therapeutic tools in experimental medicine for autologous transplantations.” Fat cells in humans might eventually be good for transplantation from the same person that provided the fat, to treat or possibly even cure their disease.

Source: Multiple Sclerosis News Today © BioNews-tx.com 2014 (23/12/14)

Placental cells appear safe for patients with MS(30/09/14)

Early evidence suggests value treatment effectiveness.

Patients with Multiple Sclerosis (MS) were able to safely tolerate treatment with cells cultured from human placental tissue, according to a study published today in the journal Multiple Sclerosis and Related Disorders. The study, which is the first of its kind, was conducted by researchers at Mount Sinai, Celgene Cellular Therapeutics subsidiary of Celgene Corporation and collaborators at several other institutions.

While designed to determine safety of the treatment, early signals in the data also suggested that a preparation of cultured cells called PDA-001 may repair damaged nerve tissues in patients with MS. PDA-001 cells resemble “mesenchymal,” stromal stem cells found in many tissues of the body. Since the cells are expanded in cell cultures, one donor is able to supply enough cells for many patients.

"This is the first time placenta-derived cells have been tested as a possible therapy for multiple sclerosis," said Fred Lublin, MD, Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Professor of Neurology at Icahn School of Medicine at Mount Sinai and the lead investigator of the study. "The next step will be to study larger numbers of MS patients to assess efficacy of the cells, but we could be looking at a new frontier in treatment for the disease."

MS is a chronic autoimmune disease in which the body's immune system mounts recurring assaults on the myelin--the fatty, protective coating around nerve fibers in the central nervous system. This causes nerves to malfunction and can lead to paralysis and blindness. The disease usually begins as an episodic disorder called relapsing-remitting MS (RRMS), and for many sufferers, evolves into a chronic condition with worsening disability called secondary progressive MS (SPMS).

The new safety study was conducted on 16 MS patients (10 with RRMS and six with SPMS) between the ages of 18 and 65. Six patients were given a high dose of PDA-001, another six were given a lower dose, and four patients were given placebo. Any time the immune system is altered, say by an experimental treatment, there is always a risk for MS to worsen, noted Dr. Lublin. All subjects were given monthly brain scans over a six-month period to ensure they did not acquire any new or enlarging brain lesions, which would indicate a worsening of MS activity. No subjects showed any paradoxical worsening on MRI and after one year, the majority had stable or improved levels of disability.

"We're hoping to learn more about how placental stromal cells contribute to myelin repair," said Dr. Lublin. "We suspect they either convert to a myelin making cell, or they enhance the environment of the area where the damage is to allow for natural repair. Our long-term goal is to develop strategies to facilitate repair of the damaged nervous system."

Collaborators in the study included the Swedish Neuroscience Institute in Seattle, WA, MultiCare Health System-Neuroscience Center of Washington, London Health Sciences Centre at University Hospital in London, the Clinical Neuroscience Research Unit at the University of Minnesota, the University of Colorado Denver, The Ottawa Hospital Multiple Sclerosis Clinic, and the MS Comprehensive Care Center at SUNY.

Dr. Fred Lublin has received research support and financial compensation as an advisory board member from Celgene, the study's sponsor.

Source: EurekaAlert! ©2014 by AAAS, the science society (30/09/14)

Early trial of stem cells for multiple sclerosis shows promise(22/09/14)

An early clinical trial testing the use of a patient's own stem cells to treat, or even reverse, multiple sclerosis has shown some positive results, Cleveland Clinic researchers reported this week.

The Phase 1 trial, unique in the United States, tested the safety and feasibility of treating MS patients with a dose of their own adult mesenchymal stem cells, or MSCs. Found in the bone marrow, MSCs are being tested in more than 150 clinical trials in the U.S. and abroad as a way to treat a variety of other conditions such as osteoarthritis, diabetes, emphysema and stroke.

Dr. Jeffrey Cohen, director of the Clinic's Mellen Center for Multiple Sclerosis Treatment and Research, presented the findings at the MSBoston2014 convention, which opened Wednesday in Boston.

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheaths that surround and protect nerve cells. When myelin is damaged, the nerve cells are exposed and unable to do their job, which is sending signals to the brain and back. This results in the loss of motor skills, coordination and cognitive abilities.

Cohen worked with a team at University Hospitals Seidman Cancer Center and Case Western Reserve University on the trial, which completed when the last patient finished the protocol in January. A total of 24 patients with relapsing forms of MS received injections of their own MSCs, which were harvested at UH, carefully cultivated in a special laboratory at CWRU and then injected intravenously back into the patient at the Clinic.

"We really encountered no practical issues and there really were no safety issues," said Cohen, noting the concern that experimental MS treatments can sometimes trigger relapse.

While the study was not designed to measure for benefit — it did not have a comparison group and involved a small group of patients — Cohen said the researchers were encouraged by what they saw.

"We didn't see any dramatic changes in anybody, but looking at the results as a whole there really were some encouraging trends, which is really as much as you hope to see in this kind of study," he said.

Cohen and his team plan a follow-up, larger Phase 2 trial that would further examine the safety of the technique but also more directly look for benefit to patients. Because of the initial positive safety results, patients in future trials won't have to come to the Clinic for visits quite as frequently for monitoring, he said.

"We had very frequent visits, lots of safety testing, so it was very difficult for someone who was not right in the area to participate," he said. "We'll be able to tone down the safety monitoring a bit so it will be a much more feasible study for trial participants to participate in."

The local team also plans a trial that will track the MSCs after they're injected, which remains an unanswered question within the stem cell field — where the cells go, where they migrate to within the body, and whether they survive. The team hopes to label the cells and track them by magnetic resonance imaging.

Both studies should be underway by next year.

Source: Cleveland.com © Plain Dealer Publishing Co. and Northeast Ohio Media Group (22/09/14)

Could reprogrammed cells fight 'untreatable' diseases?(28/08/14)

Jeanne Loring and her Scripps Research Institute colleagues transplanted a set of cells into the spinal cords of mice that had lost use of their hind limbs to multiple sclerosis. As the experimentalists expected, within a week, the mice rejected the cells. But after another week, the mice began to walk.

“We thought that they wouldn’t do anything,” says Loring, who directs the Center for Regenerative Medicine at Scripps. But as her lab has since shown numerous times, and published in Stem Cell Reports, something that these particular so-called “neural precursor cells” do before the immune system kicks them out seems to make the mouse better.

The cells Loring’s team used are derived from induced pluripotent stem cells, which are mature cells, such as skin cells, that have been coaxed with a combination of chemicals to return to an earlier stage of development.

Induced pluripotent cells, also known as iPS cells, pose a number of opportunities for medicine. For instance, Loring is using iPS cells from Parkinson’s disease and multiple sclerosis patients to reconstitute cell types that may be damaged in people with those conditions. She is also using them to test how certain drugs or treatments may affect damaged cells in people with conditions such as autism spectrum disorders.

Loring says no viable long-term treatments exist for the diseases her team has been working on, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, “That’s where the need is,” she says.

The neural precursor cells that Loring has been using in the mice with MS are young cells that haven’t quite gotten to the point of being nerves yet. Only certain types of these cells have such a dramatic Lazarus-like effect on the affected mice, but Loring’s team can readily identify them based on DNA analysis.

Even so, they’re not yet ready to treat human MS patients with the approach, she says. First, the researchers want to identify what the cells produce—a protein, perhaps, or a set of proteins—that allows the mice to walk.

For other diseases, however, researchers are closer to being ready to transplant working versions of reprogrammed cells into sick people.

For instance, Loring is exploring whether it’s possible to reprogram skin cells from patients with Parkinson’s disease so they turn into iPS cells and then into working dopamine neurons, which are the cells affected in the disease.

It seems to work in animals: Loring’s lab has transformed skin cells from eight human Parkinson’s disease patients into iPS cells and transplanted them as neurons into animal models.

A local Southern California Parkinson’s disease association has funded the research so far. Now Loring and colleagues are seeking additional funds to move through regulatory approval and toward the clinic.

Meanwhile, iPS cells separately suggest a way to test how disease-affected cells may or may not respond to treatment in diseases like autism, by in effect creating “dummy” cells on which drugs could be tested.

After making iPS cells from the cells of fragile X syndrome patients, a genetic condition that often co-occurs with some forms of autism, Loring’s lab turned them into cortical neurons—cells that she suspects don’t develop as they should in people with the disorder.

Indeed, the cortical neurons her lab grew from those iPS cells looked different than other cortical neurons and suffered delayed development. These neurons, she explains, could be used to test different molecules and compounds to see whether drugs could treat cells affected by autism.

This sort of approach, in which so-called “derived cells” are used for drug screening, Loring said, is the likely way that iPS cells will first be used in medicine, especially as more and more people have their genomes analyzed. Treatment with reprogrammed iPS cells will take longer to develop.

Loring says she hopes soon to be able to set up simple assays “that will allow us to find out what sort of drugs will work for people with particular genotypes.” That could offer a significant boost to drug development. iPS cells are an important new opportunity to attack diseases that otherwise have vexed researchers and doctors for decades.

Source: Techonomy © Forbes 2014 (28/08/14)

Scientists one step closer to cell therapy for multiple sclerosis patients(25/07/14)

Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute are one step closer to creating a viable cell replacement therapy for multiple sclerosis from a patient's own cells.

For the first time, NYSCF scientists generated induced pluripotent stem (iPS) cells lines from skin samples of patients with primary progressive multiple sclerosis and further, they developed an accelerated protocol to induce these stem cells into becoming oligodendrocytes, the myelin-forming cells of the central nervous system implicated in multiple sclerosis and many other diseases.

Existing protocols for producing oligodendrocytes had taken almost half a year to produce, limiting the ability of researchers to conduct their research. This study has cut that time approximately in half, making the ability to utilize these cells in research much more feasible.

Stem cell lines and oligodendrocytes allow researchers to "turn back the clock" and observe how multiple sclerosis develops and progresses, potentially revealing the onset of the disease at a cellular level long before any symptoms are displayed. The improved protocol for deriving oligodendrocyte cells will also provide a platform for disease modeling, drug screening, and for replacing the damaged cells in the brain with healthy cells generated using this method.

"We are so close to finding new treatments and even cures for MS. The enhanced ability to derive the cells implicated in the disease will undoubtedly accelerate research for MS and many other diseases," said Susan L. Solomon, NYSCF Chief Executive Officer.

"We believe that this protocol will help the MS field and the larger scientific community to better understand human oligodendrocyte biology and the process of myelination. This is the first step towards very exciting studies: the ability to generate human oligodendrocytes in large amounts will serve as an unprecedented tool for developing remyelinating strategies and the study of patient-specific cells may shed light on intrinsic pathogenic mechanisms that lead to progressive MS". said Dr. Valentina Fossati, NYSCF – Helmsley Investigator and senior author on the paper.

In multiple sclerosis, the protective covering of axons, called myelin, becomes damaged and lost. In this study, the scientists not only improved the protocol for making the myelin-forming cells but they showed that the oligodendrocytes derived from the skin of primary progressive patients are functional, and therefore able to form their own myelin when put into a mouse model. This is an initial step towards developing future autologous cell transplantation therapies in multiple sclerosis patients.

This important advance opens up critical new avenues of research to study multiple sclerosis and other diseases. Oligodendrocytes are implicated in many different disorders, therefore this research not only moves multiple sclerosis research forward, it allows NYSCF and other scientists the ability to study all demyelinating and central nervous system disorders.

"Oligodendrocytes are increasingly recognized as having an absolutely essential role in the function of the normal nervous system, as well as in the setting of neurodegenerative diseases,such as multiple sclerosis. The new work from the NYSCF Research Institute will help to improve our understanding of these important cells. In addition, being able to generate large numbers of patient-specific oligodendrocytes will support both cell transplantation therapeutics for demyelinating diseases and the identification of new classes of drugs to treat such disorders," said Dr. Lee Rubin, NYSCF Scientific Advisor and Director of Translational Medicine at the Harvard Stem Cell Institute.

Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system, distinguished by recurrent episodes of demyelination and the consequent neurological symptoms. Primary progressive multiple sclerosis is the most severe form of multiple sclerosis, characterized by a steady neurological decline from the onset of the disease. Currently, there are no effective treatments or cures for primary progressive multiple sclerosis and treatments relies merely on symptom management.

NYSCF stem cell researcher Valentina Fossati, PhD, is the senior author and NYSCF researcher Panagiotis Douvaras, PhD, is the first author of this study.

Key collaborators on this research included Dr. Saud Sadiq and the Tisch Multiple Sclerosis Research Center of New York where patients were recruited, Dr. Fraser Sim of the State University of New York at Buffalo for the in vivo studies, and Dr. James Goldman of Columbia University Medical Center.

The New York Stem Cell Foundation research was supported by a NYSCF – Helmsley Early Career Investigator Award, The New York Stem Cell Foundation, and The Leona M. and Harry B. Helmsley Charitable Trust. The in vivo studies were supported by the Empire State Stem Cell Fund through New York State Department of Health.

Source: EurekaAlert Copyright ©2014 by AAAS, the science society (25/07/14)

'Master switch' for myelination in human brain stem cells is identified(01/07/14)

Scientists at the University at Buffalo have identified the single transcription factor or "master switch" that initiates the critical myelination process in the brain. The research will be published online in Proceedings of the National Academy of Sciences (PNAS) on June 30.

The identification of this factor, SOX10, in human brain cells, brings researchers closer to the goal of treating multiple sclerosis (MS) by transplanting into patients the brain cells that make myelin.

"Now that we have identified SOX10 as an initiator of myelination, we can work on developing a viral or pharmaceutical approach to inducing it in MS patients," says Fraser Sim, PhD, senior author on the paper and assistant professor in the UB Department of Pharmacology and Toxicology in the School of Medicine and Biomedical Sciences.

"If we could create a small molecule drug that would switch on SOX10, that would be therapeutically important," he adds.

Stem cell therapy is seen as having dramatic potential for treating MS, but there are key obstacles, especially the length of time it takes for progenitor cells to turn into oligodendrocytes, the brain's myelin-making cells.

Using currently available methods, Sim explains, it can take as long as a year to generate a sufficient number of human oligodendrocyte cells to treat a single MS patient. That's partly because there are so many steps: the skin or blood cell must be turned into induced pluripotent stem cells, which can differentiate into any other type of cell and from which neural progenitor cells can be produced. Those progenitor cells then must undergo differentiation to oligodendrocyte progenitors that are capable of ultimately producing the oligodendrocytes.

"Ideally, we'd like to get directly to oligodendrocyte progenitors," says Sim. "The new results are a stepping stone to the overall goal of being able to take a patient's skin cells or blood cells and create from them oligodendrocyte progenitors," he says.

Using fetal (not embryonic) brain stem cells, the UB researchers searched for transcription factors that are absent in neural progenitor cells and switched on in oligodendrocyte progenitor cells.

While neural progenitor cells are capable of producing myelin, they do so very poorly and can cause undesirable outcomes in patients, so the only candidate for transplantation is the oligodendrocyte progenitor.

"The ideal cell to transplant is the oligodendrocyte progenitor cell," Sim says. "The question was, could we use one of these transcription factors to turn the neural progenitor cell into an oligodendrocyte progenitor cell?"

To find out, they looked at different characteristics, such as mRNA expression, protein and whole gene expression and functional studies.

"We narrowed it down to a short list of 10 transcription factors that were made exclusively by oligodendrocyte progenitor cells," says Sim. "Among all 10 factors that we studied, only SOX10 was able to make the switch from neural progenitor to oligodendrocyte progenitor cell," says Sim.

In addition, the UB researchers found that SOX10 could expedite the transformation from oligodendrocyte progenitor cell to differentiation as an oligodendrocyte, the myelin-producing cell and the ultimate treatment goal for MS.

"SOX10 facilitates both steps," says Sim.

That's tantalizing, he says, because one of the biggest problems with MS is that cells get stuck in the step between the oligodendrocyte progenitor cell and the oligodendrocyte. "In MS, first the immune system attacks the brain, but the brain is unable to repair itself effectively," explains Sim. "If we could boost the regeneration step by facilitating formation of oligodendrocytes from progenitor cells, then we might be able to keep patients in the relapsing remitting stage of MS, a far less burdensome stage of disease than the later, progressive stage."

Sim is also an investigator with other scientists at UB and the University of Rochester on the $12.1 million New York State Stem Cell Science award led by SUNY Upstate Medical Center. The research will test the safety and effectiveness of implanting stem cells that can reproduce myelin into the central nervous system of MS patients.

Source: Medical Xpress © Medical Xpress 2011-2014 (01/07/14)

Future embryonic stem cell treatment promise for multiple sclerosis(19/06/14)

Scientists in the University of Connecticut's Technology Incubation Program have identified a novel approach to treating multiple sclerosis (MS) using human embryonic stem cells, offering a promising new therapy for more than 2.3 million people suffering from the debilitating disease.

The researchers demonstrated that the embryonic stem cell therapy significantly reduced MS disease severity in animal models, and offered better treatment results than stem cells derived from human adult bone marrow.

The study was led by ImStem Biotechnology Inc. of Farmington, Conn., in conjunction with UConn Health Professor Joel Pachter, Assistant Professor Stephen Crocker, and Advanced Cell Technology (ACT) Inc. of Massachusetts. ImStem was founded in 2012 by UConn doctors Xiaofang Wang and Ren-He Xu, along with Yale University doctor Xinghua Pan and investor Michael Men.

"The cutting-edge work by ImStem, our first spinoff company, demonstrates the success of Connecticut's Stem Cell and Regenerative Medicine funding program in moving stem cells from bench to bedside," says Professor Marc Lalande, director of the UConn's Stem Cell Institute.

The research was supported by a $1.13 million group grant from the state of Connecticut's Stem Cell Research Program that was awarded to ImStem and Professor Pachter's lab.

"Connecticut's investment in stem cells, especially human embryonic stem cells, continues to position our state as a leader in biomedical research," says Gov. Dannel P. Malloy. "This new study moves us one step closer to a stem cell-based clinical product that could improve people's lives."

"The cutting-edge work by ImStem ... demonstrates the success of Connecticut's Stem Cell and Regenerative Medicine funding program in moving stem cells from bench to bedside. - Marc Lalande"

The researchers compared eight lines of adult bone marrow stem cells to four lines of human embryonic stem cells. All of the bone marrow-related stem cells expressed high levels of a protein molecule called a cytokine that stimulates autoimmunity and can worsen the disease. All of the human embryonic stem cell-related lines expressed little of the inflammatory cytokine.

Another advantage of human embryonic stem cells is that they can be propagated indefinitely in lab cultures and provide an unlimited source of high quality mesenchymal stem cells - the kind of stem cell needed for treatment of MS, the researchers say. This ability to reliably grow high quality mesenchymal stem cells from embryonic stem cells represents an advantage over adult bone marrow stem cells, which must be obtained from a limited supply of healthy donors and are of more variable quality.

"Groundbreaking research like this furthering opportunities for technology ventures demonstrates how the University acts as an economic engine for the state and regional economy," says Jeff Seemann, UConn's vice president for research.

The findings also offer potential therapy for other autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and type-1 diabetes, according to Xu, a corresponding author on the study and one of the few scientists in the world to have generated new human embryonic stem cell lines.

There is no cure for MS, a chronic neuroinflammatory disease in which the body's immune system eats away at the protective sheath called myelin that covers the nerves. Damage to myelin interferes with communication between the brain, spinal cord, and other areas of the body. Current MS treatments only offer pain relief, and slow the progression of the disease by suppressing inflammation.

"The beauty of this new type of mesenchymal stem cells is their remarkable higher efficacy in the MS model," says Wang, chief technology officer of ImStem.

Source: MNT © MediLexicon International Ltd 2004-2014 (19/06/14)/p>

Walking mice kick off new area of MS stem cell research(12/05/14)

Mice severely disabled by a multiple sclerosis (MS)-like condition could walk less than two weeks following treatment with human stem cells. The finding, which uncovers new avenues for treating MS, will be published online in the journal Stem Cell Reports.

When scientists transplanted human stem cells into MS mice, they predicted the cells would be rejected, much like rejection of an organ transplant.

Expecting no benefit to the mice, they were surprised when the experiment yielded spectacular results.

"My postdoctoral fellow Dr. Lu Chen came to me and said, 'The mice are walking.' I didn't believe her," said co-senior author, Tom Lane, a professor of pathology at the University of Utah, who began the work at University of California, Irvine.

Within just 10 to 14 days, the mice regained motor skills. Six months later, they still showed no signs of slowing down.

"This result opens up a whole new area of research for us," said co-senior author Jeanne Loring, co-senior author and professor at The Scripps Research Institute in La Jolla, Calif.

More than 2.5 million people worldwide have MS, a disease where the immune system attacks myelin, an insulation layer surrounding nerve fibres. The resulting damage inhibits nerve impulses, producing symptoms that include difficulty walking, impaired vision, fatigue and pain.

The MS mice treated with human stem cells experience a reversal of symptoms. Immune attacks are blunted, and damaged myelin is repaired, explaining their dramatic recovery. The discovery could help patients with latter, or progressive, stages of the disease, for whom there are no treatments.

Counterintuitively, the researchers' original prediction that the mice would reject the stem cells, came true. There are no signs of the cells after one week. In that short window, they send chemical signals that instruct the mouse's own cells to repair the damage caused by MS. This realisation could be important for therapy development.

"Rather than having to engraft stem cells into a patient, which can be challenging, we might be able to put those chemical signals into a drug that can be used to deliver the therapy much more easily," said Lane.

With clinical trials as the long-term goal, the next steps are to assess durability and safety of the stem cell therapy in mice.

"I would love to see something that could promote repair and ease the burden that patients with MS have," said Lane.

Source: University of Utah Health Sciences (12/05/14)

Autologous haematopoietic stem cell transplantation for aggressive MS: the Swedish experience(28/04/14)

Abstract

BACKGROUND: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.

METHODS: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.

RESULTS: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).

CONCLUSIONS: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.

Burman J, Iacobaeus E, Svenningsson A, Lycke J, Gunnarsson M, Nilsson P, Vrethem M, Fredrikson S, Martin C, Sandstedt A, Uggla B, Lenhoff S, Johansson JE, Isaksson C, Hägglund H, Carlson K, Fagius J.

Sources: J Neurol Neurosurg Psychiatry. 2014 Feb 19. doi: 10.1136/jnnp-2013-307207 & Pubmed PMID: 24554104 (28/04/14)

Multiple sclerosis umbilical cord stem cell therapy clinical trial approved(03/04/14)

Translational Biosciences, a subsidiary of Medistem Panama, has received the green light for a phase I/II clinical trial using human umbilical cord-derived mesenchymal stem cells (UC-MSC) for multiple sclerosis from the Comité Nacional de Bioética de la Investigación (CNEI) Institutional Review Board (IRB) in Panama.

According to the US National Multiple Sclerosis Society, in Multiple Sclerosis (MS), an abnormal immune-mediated T cell response attacks the myelin coating around nerve fibers in the central nervous system, as well as the nerve fibers themselves. This causes nerve impulses to slow or even halt, thus producing symptoms of MS that include fatigue; bladder and bowel problems; vision problems; and difficulty walking. The Cleveland Clinic reports that MS affects more than 350,000 people in the United States and 2.5 million worldwide.

Mesenchymal stem cells harvested from donated human umbilical cords after normal, healthy births possess anti-inflammatory and immune modulatory properties that may relieve MS symptoms. Because these cells are immune privileged, the recipient’s immune system does not reject them. These properties make UC-MSC interesting candidates for the treatment of multiple sclerosis and other autoimmune disorders.

Each patient will receive seven intravenous injections of UC-MSC over the course of 10 days. They will be assessed at 3 months and 12 months primarily for safety and secondarily for indications of efficacy.

The stem cell technology being utilised in this trial was developed by Neil Riordan, PhD, founder of Medistem Panama. The stem cells will be harvested and processed at Medistem Panama’s 8000 sq. ft. ISO-9001 certified laboratory in the prestigious City of Knowledge. They will be administered at the Stem Cell Institute in Panama City, Panama.

From his research laboratory in Dallas, Texas, Dr. Riordan commented, “Umbilical cord tissue provides an abundant, non-controversial supply of immune modulating mesenchymal stem cells. Preclinical and clinical research has demonstrated the anti-inflammatory and immune modulating effects of these cells. We look forward to the safety and efficacy data that will be generated by this clinical trial; the first in the western hemisphere testing the effects of umbilical cord mesenchymal stem cells on patients with multiple sclerosis.”

The Principle Investigator is Jorge Paz-Rodriguez, MD. Dr. Paz-Rodriguez also serves as the Medical Director at the Stem Cell Institute. For detailed information about this clinical trial visit http://www.clinicaltrials.gov.

Source: PR Web ©Copyright 1997-2014, Vocus PRW Holdings, LLC (03/04/14)

Stem cells from muscle may repair nerve damage due to MS - study(20/03/14)

Stem cells derived from human muscle tissue were able to repair nerve damage and restore function in an animal model of sciatic nerve injury, according to researchers at the University of Pittsburgh School of Medicine. The findings, published online today in the Journal of Clinical Investigation, suggest that cell therapy of certain nerve diseases, such as multiple sclerosis, might one day be feasible.

To date, treatments for damage to peripheral nerves, which are the nerves outside the brain and spinal cord, have not been very successful, often leaving patients with impaired muscle control and sensation, pain and decreased function, said senior author Johnny Huard, Ph.D., professor of orthopaedic surgery, and Henry J. Mankin Chair in Orthopaedic Surgery Research, Pitt School of Medicine, and deputy director for cellular therapy, McGowan Institute for Regenerative Medicine.

"This study indicates that placing adult, human muscle-derived stem cells at the site of peripheral nerve injury can help heal the lesion," Dr. Huard said. "The stem cells were able to make non-neuronal support cells to promote regeneration of the damaged nerve fiber."

The researchers, led by Dr. Huard and Mitra Lavasani, Ph.D., first author and assistant professor of orthopaedic surgery, Pitt School of Medicine, cultured human muscle-derived stem/progenitor cells in a growth medium suitable for nerve cells. They found that, with prompting from specific nerve-growth factors, the stem cells could differentiate into neurons and glial support cells, including Schwann cells that form the myelin sheath around the axons of neurons to improve conduction of nerve impulses.

In mouse studies, the researchers injected human muscle-derived stem/progenitor cells into a quarter-inch defect they surgically created in the right sciatic nerve, which controls right leg movement. Six weeks later, the nerve had fully regenerated in stem-cell treated mice, while the untreated group had limited nerve regrowth and functionality. Twelve weeks later, treated mice were able to keep their treated and untreated legs balanced at the same level while being held vertically by their tails. When the treated mice ran through a special maze, analyses of their paw prints showed eventual restoration of gait. Treated and untreated mice experienced muscle atrophy, or loss, after nerve injury, but only the stem cell-treated animals had regained normal muscle mass by 72 weeks post-surgery.

"Even 12 weeks after the injury, the regenerated sciatic nerve looked and behaved like a normal nerve," Dr. Lavasani said. "This approach has great potential for not only acute nerve injury, but also conditions of chronic damage, such as diabetic neuropathy and multiple sclerosis."

Drs. Huard and Lavasani and the team are now trying to understand how the human muscle-derived stem/progenitor cells triggered injury repair, as well as developing delivery systems, such as gels, that could hold the cells in place at larger injury sites.

Journal Reference:
Mitra Lavasani, Seth D. Thompson, Jonathan B. Pollett, Arvydas Usas, Aiping Lu, Donna B. Stolz, Katherine A. Clark, Bin Sun, Bruno Péault, Johnny Huard. Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI44071

Source: Science Daily Copyright 2014 by ScienceDaily, LLC (20/03/14)

Push for Australia to provide multiple sclerosis treatment (26/02/14)

Patients who have used stem cell therapy to reverse the effects of multiple sclerosis are lobbying the Federal Government to provide the treatment in Australia.

A European trial has achieved a 95 per cent success rate, but Australian hospitals are reluctant to use it.

The treatment involves using haematopoietic stem cell therapy, where a patient’s stem cells are harvested from their blood, then an intense chemotherapy regime kills off the MS-ridden immune system, before the harvested stem cells are reinjected.

Neurologist Dr Colin Andrews was one of the first in Australia to use the treatmen, which is only suitable for patients with aggressive MS that existing medication cannot treat.

“We're rebooting the immune system and moving the cells we don’t want,” Dr Andrews said.

“Within a week to 10 days you've got a whole new immune system.”

Recent overseas studies have had a 95 percent success rate of stopping the disease.

The first eight patients in Australia had the treatment done at Canberra Hospital, but the hospital shut down the program half way through the ninth patient on the grounds it was unethical.

“What we’re doing here is harvesting the patient’s own cells, it’s not cells from elsewhere or any other source, so I can’t see there's an ethical issue,” Dr Andrews said. It leaves only one doctor in Australia offering the treatment, yet there are about 4000 sufferers, leaving many heading overseas for help.

But it is at huge cost.

“I had no choice, I was on a ticking time bomb, I didn’t know what to expect next, my health and my child is far more important so I had to go,” Melinda Beattie said.

She spent $65,000 to go to India for the treatment, while Andrew Price flew to the US spending $130,000.

Both their treatments were successful.

They've now formed an organisation to lobby the Federal Government, but MS Australia is refusing to support it at the current time.

“The procedure itself is still in a very experimental stage very much only works with a very small number of people,” Deb Cerasa from MS Australia said.

But Dr Andrews has defended the treatment.

“It’s a procedure, it’s not an experiment, something that’s been around for 10 years, it’s widely practiced throughout the rest of the world we don’t regard it as experimental,” he said.

Source: Yahoo! 7 News (26/02/14)

Extensive renewal of the T cell repertoire following autologous stem cell transplant in MS(18/02/14)

A new study describes the complexity of the new T cell repertoire following immune-depleting therapy to treat multiple sclerosis, improving our understanding of immune tolerance and clinical outcomes.

In the Immune Tolerance Network's (ITN) HALT-MS study, 24 patients with relapsing, remitting multiple sclerosis received high-dose immunosuppression followed by a transplant of their own stem cells, called an autologous stem cell transplant, to potentially reprogram the immune system so that it stops attacking the brain and spinal cord. Data published today in the Journal of Clinical Investigation quantified and characterized T cell populations following this aggressive regimen to understand how the reconstituting immune system is related to patient outcomes.

ITN investigators used a high-throughput, deep-sequencing technology (Adaptive Biotechnologies, ImmunoSEQTM Platform) to analyze the T cell receptor (TCR) sequences in CD4+ and CD8+ cells to compare the repertoire at baseline pre-transplant, two months post-transplant and 12 months post-transplant.

Using this approach, alongside conventional flow cytometry, the investigators found that CD4+ and CD8+ lymphocytes exhibit different reconstitution patterns following transplantation. The scientists observed that the dominant CD8+ T cell clones present at baseline were expanded at 12 months post-transplant, suggesting these clones were not effectively eradicated during treatment. In contrast, the dominant CD4+ T cell clones present at baseline were undetectable at 12 months, and the reconstituted CD4+ T cell repertoire was predominantly comprised of new clones.

The results also suggest the possibility that differences in repertoire diversity early in the reconstitution process might be associated with clinical outcomes. Nineteen patients who responded to treatment had a more diverse repertoire two months following transplant compared to four patients who did not respond. Despite the low number of non-responders, these comparisons approached statistical significance and point to the possibility that complexity in the T cell compartment may be important for establishing immune tolerance.

This is one of the first studies to quantitatively compare the baseline T cell repertoire with the reconstituted repertoire following autologous stem cell transplant, and provides a previously unseen in-depth analysis of how the immune system reconstitutes itself following immune-depleting therapy.

Source: Medical Xpress © Medical Xpress 2011-2014, Science X network (18/02/14)

Stem cell 'major discovery' claimed(31/01/14)

Stem cell researchers are heralding a "major scientific discovery", with the potential to start a new age of personalised medicine.

Scientists in Japan showed stem cells can now be made quickly just by dipping blood cells into acid.

Stem cells can transform into any tissue and are already being trialled for healing the eye, heart and brain.

The latest development, published in the journal Nature, could make the technology cheaper, faster and safer.

The human body is built of cells with a specific role - nerve cells, liver cells, muscle cells - and that role is fixed.

However, stem cells can become any other type of cell, and they have become a major field of research in medicine for their potential to regenerate the body.

Embryos are one, ethically charged, source of stem cells. Nobel prize winning research also showed that skin cells could be "genetically reprogrammed" to become stem cells (termed induced pluripotent stem cells).

Acid bath
Now a study shows that shocking blood cells with acid could also trigger the transformation into stem cells - this time termed STAP (stimulus-triggered acquisition of pluripotency) cells.

Dr Haruko Obokata, from the Riken Centre for Developmental Biology in Japan, said she was "really surprised" that cells could respond to their environment in this way.

She added: "It's exciting to think about the new possibilities these findings offer us, not only in regenerative medicine, but cancer as well."

The breakthrough was achieved in mouse blood cells, but research is now taking place to achieve the same results with human blood.

Chris Mason, professor of regenerative medicine at University College London, said if it also works in humans then "the age of personalised medicine would have finally arrived."

He told the BBC: "I thought - 'my God that's a game changer!' It's a very exciting, but surprise, finding.

"It looks a bit too good to be true, but the number of experts who have reviewed and checked this, I'm sure that it is.

"If this works in people as well as it does in mice, it looks faster, cheaper and possibly safer than other cell reprogramming technologies - personalised reprogrammed cell therapies may now be viable."

For age-related macular degeneration, which causes sight loss, it takes 10 months to go from a patient's skin sample to a therapy that could be injected into their eye -and at huge cost.

Prof Mason said weeks could be knocked off that time which would save money, as would cheaper components.

'Revolutionary'
The finding has been described as "remarkable" by the Medical Research Council's Prof Robin Lovell-Badge and as "a major scientific discovery" by Dr Dusko Ilic, a reader in stem cell science at Kings College London.

Dr Ilic added: "The approach is indeed revolutionary.

"It will make a fundamental change in how scientists perceive the interplay of environment and genome."

But he added: "It does not bring stem cell-based therapy closer. We will need to use the same precautions for the cells generated in this way as for the cells isolated from embryos or reprogrammed with a standard method."

And Prof Lovell-Badge said: "It is going to be a while before the nature of these cells are understood, and whether they might prove to be useful for developing therapies, but the really intriguing thing to discover will be the mechanism underlying how a low pH shock triggers reprogramming - and why it does not happen when we eat lemon or vinegar or drink cola?"

Source: BBC News © British Broadcasting Corporation 2014 (31/01/14)

StemGenex® continues to announce groundbreaking stem cell therapies for MS patients(03/12/13)

New targeted stem cell therapy looks to improve MS patients dealing with incontinence complications.

StemGenex®, the leading resource for adult adipose stem cell therapy in the US aimed at improving the lives of patients dealing with degenerative diseases today announced the newest therapy to assist patients diagnosed with Multiple Sclerosis.

According to the National MS Society, at least 80% of people with MS experience bladder dysfunction. StemGenex believes a new therapy delivering adipose derived mesenchymal cells directly to the bladder may reduce the inflammation that is causing the patient’s incontinence.

Direct bladder targeting is the latest in a series of targeted therapies StemGenex® plans to announce in the next few months for patients dealing with degenerative diseases such as Parkinson’s, Alzheimer’s, COPD and of course Multiple Sclerosis. Earlier this month StemGenex announced a new intranasal stem cell therapy. The goal of this new technique is to encourage more stem cells to travel through the blood brain barrier to target the damage caused by MS.

Stem cell treatment studies are currently being offered by StemGenex to patients diagnosed with Multiple Sclerosis and other degenerative neurological diseases. StemGenex takes a unique approach of compassion and empowerment while providing access to the latest stem cell therapies for degenerative neurological diseases including Parkinson’s and Alzheimer’s disease, stroke recovery and others. Rita Alexander, founder of StemGenex and the company’s first stem cell patient, insists that all patients be treated like they are one of our loved ones. "Hope, compassion, and the relentless pursuit for an end to these diseases are our primary focus."

Source: © Copyright 1997-2013, Vocus PRW Holdings, LLC. Vocus, PRWeb (03/12/13)

Ottawa doctors behind breakthrough multiple sclerosis study(18/11/13)

A team of Ottawa doctors is preparing to publish a full report on its breakthrough multiple sclerosis treatment study that has so far eliminated the disease in those treated.

The experimental study began about 13 years ago as a last resort for patients who fail to improve on drug therapy and who suffer severe symptoms of MS. Snippets of the results have been published “here and there,” said, neurologist Dr. Mark Freedman, one of the leads of the program at The Ottawa Hospital, but its never been published in its entirety.

No specific date has been set for its release, but the team’s findings are far from secret. With MS not returning in any of the 24 participants, patient success stories appear in news media across the country. Since the original study’s completion, about another dozen patients have been treated with all of them showing the same results.

Eliminating MS completely and watching patients improve surprised both Freedman and Dr. Harold Atkins, a bone-marrow transplant expert, who started the study. The two originally set out to monitor the development of the disease and find a way to treat it. Their theory was this: Wipe out the entire immune system, reboot it with a transplant of the patient’s own bone marrow and wait for MS to regenerate.

“We thought we might be able to intercept one of the signals that initiates the disease and that would then give us a clue on how to treat it,” Freedman said. He jokes that they “had, in effect, failed because the disease never came back. No one expected to see zero disease activity after the transplant.”

Patients from Vancouver to Newfoundland, who had given up hope, became part of the original 24, including third-year medical student Alex Normandin from Montreal.

The aspiring doctor noticed alarming symptoms of fatigue, numbness and problems with balance and co-ordination. Researchers at the Montreal Neurological Institute confirmed he has a particularly aggressive form of MS, an unpredictable and degenerative disease that affects the central nervous system.

Most patients do not become severely disabled because the illness moves slowly. But in Normandin’s case, the destruction was so fast that doctors expected him to need a wheelchair within months.

Normandin, however, learned of the cutting-edge treatment run by Freedman and Atkins. He became patient No. 19 in the experiment and had his transplant in Ottawa in December 2008.

The procedure has its risks. One patient died in an earlier phase of the trial. It was in 2001 or 2002, Freedman recalled, saying the death was due to the pill form of the drug Busulphan. Used early on in the experiment, the drug attacks the liver twice, both when it enters the body and again when it leaves. But within a year, the team had found that a new intravenous version of the drug improved patient safety tremendously.

Freedman had the task of trying to scare patients by telling them the risks.

“My job was to talk everybody out of it,” he said. “It really is the hardest thing they’ll have to do in their lives. It is a bit of a gamble, but with the fantastic team we have in Ottawa, it’s less of a gamble.”

All participants showed dramatic improvement, and none reported relapses, according to a study on the Freedman-Atkins treatment by a team of MS researchers at the Neuro and the Université de Montréal.

Plus, magnetic resonance imaging (MRI) showed no new lesions in the brain, “no new MS disease activity,” according to findings published in the latest issue of Annals of Neurology.

For Normandin, he’s now a family physician in private practice on the West Island and no longer takes medication for the illness. His fatigue and balance problems continue to diminish daily.

But despite such dramatic results, none of the MS researchers in this study is calling the procedure a cure.

For one thing, it is not known whether the treatment is good at stopping other kinds of MS, explained neurologist Amit Bar-Or of the Montreal Neurological Institute and McGill University and the study’s principal investigator.

Also, bone-marrow stem-cell transplants to treat MS are not approved outside of clinical trials because while the disease itself is not deadly, the procedure is fatal in as much as five per cent of patients.

But Freedman questions the risk rate. He says the five-per-cent figure was from data collected in the 1990s as the team prepared for the experiment. That number has since dropped to about one per cent, he said.

In addition to medical advancements, by comparing the immune responses in patients before and after the treatment, researchers discovered a key biological target for new therapies that might be able to provide similar benefits without the risks associated with knocking out someone’s immune system to facilitate a bone-marrow transplant.

Several studies have already noted that in MS patients, the body’s immune system attacks its own cells. Overactive T cells (a type of white blood cells called lymphocytes) — that are responsible for defending the body against bacteria, viruses and other parasites — can also damage myelin, the protective insulation covering nerves.

The concept is straightforward, Bar-Or explained. To fight an infection, different types of T cells mount a quick response, then other T cells quickly ratchet back that response, he said. But in auto-immune conditions, including MS, this regulation goes awry and the body attacks itself.

Researchers have zeroed in on a particular subset of T cells, called TH17 cells, that have a substantially diminished function following the experimental transplant. The discovery could help researchers target treatment in MS patients generally.

“We are cautious in not claiming we have figured out all cells responsible for all relapses in all MS patients,” Bar-Or noted. “Keep in mind these patients have very aggressive MS, so maybe TH17 are particularly important in these patients.”

Emerging treatments, however, are already attempting to target TH17 cells, but the story is even more complicated, Bar-Or said.

“We don’t know everything about them (TH17 cells) even in terms of basic immunology. It’s likely that within the TH17 subset there may be particular bad guys ... It would be nice to know which because we need to have these cells some of the time. Getting rid of all of them all of the time, may not be completely safe.”

Both the clinical study at the Ottawa Hospital Multiple Sclerosis Research Unit and biological study in Montreal were funded by the Research Foundation of the Multiple Sclerosis Society of Canada.

Canada has one of the highest rates of MS in the world — affecting about 55,000 to 75,000 people.

Normandin says his illness has been a blessing in disguise, giving him a unique perspective not found in medical text books.

“It changed my whole outlook on life. It definitely affects the way I see patients. I’m more sensitive in how to talk to them and more empathetic dealing with chronic diseases.”

He was once on a career track where the focus was work, but now “life balance” is everything and he is grateful for the treatment that gave him his life back and allowed him to work in a clinic where he can spend as much time as necessary talking to patients.

“Life is great,” he said. “I love to say it.”

Source: The Ottawa Citizen © Copyright (c) The Ottawa Citizen 2013 (18/11/13)