A study, Human Placenta-Derived Cells (PDA-001) For The Treatment Of Adults With Multiple Sclerosis: A Randomised, Placebo-Controlled, Multiple-Dose Study, published in the journal Multiple Sclerosis and Related Disorders and led by researchers at Mount Sinai in New York and Celgene Cellular Therapeutics, has revealed an infusion based on cells derived from the placenta proved to be safe for patients with multiple sclerosis and a promising new treatment for the condition.
It has been previously shown that therapeutic cell-based infusions have an immunomodulatory and repair action in MS. PDA-001 in particular is a preparation of cultured mesenchymal-like cells derived from healthy human placental tissue and designed for the treatment of MS as these cells have immunomodulatory, anti-inflammatory, pro-regenerative and neuroprotective properties. As these placenta cells are expanded in cell culture, one healthy donor is capable of supplying enough cells for several patients.
In the study, researchers tested the safety and possible exacerbation of the disease with this new MS treatment approach based on PDA-001. A phase 1b, randomised, multi-centre, double-blind, placebo-controlled study was conducted with 16 MS patients (ten with relapsing-remitting MS and six with secondary progressive MS), aged between 18 and 65 years. Six patients received a high dose of PDA-001 (600×106 cells), other six were given a lower dose (150×106 cells), and the remaining four patients received a placebo. Patients were monitored monthly for brain lesions.
Researchers found none of the patients had worsening of MS-related brain lesions one year after treatment with both PDA-001 doses, and the majority of the patients had stable or had improved levels of disability.
“We’re hoping to learn more about how placental stromal cells contribute to myelin repair,” said the study’s lead author and Professor of Neurology at Mount Sinai, Dr Fred Lublin in a news release.
“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.”
The research team concluded that PDA-001 treatment was overall safe and well tolerated by patients, and that preliminary evidence suggests that PDA-001 could be able to repair damaged nerve tissues in MS patients.
“This is the first time placenta-derived cells have been tested as a possible therapy for multiple sclerosis,” said Dr Lublin.
“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.”
Source: Multiple Sclerosis News Today © BioNews Services 2015 (06/05/15)
A common athlete’s foot cream sold over the counter at most chemists could help people living with multiple sclerosis, a new study claims.
Researchers believe the drug miconazole - the active ingredient in Daktarin - instructs stem cells in the brain to repair nerve damage. The discovery comes after a team at Case Western Reserve University in Ohio tested more than 700 drugs to see if anyone would be useful against MS.
The athlete’s foot drug and a cream used to treat eczema were found to stimulate the regeneration of damaged brain cells. It was found to reverse paralysis in mice.
"We know that there are stem cells throughout the adult nervous system that are capable of repairing the damage caused by multiple sclerosis, but until now we had no way to direct them to act," said Dr Paul Tesar, Professor of Innovative Therapeutics at Case Western Reserve School of Medicine.
"Our approach was to find drugs that could catalyse the body's own stem cells to replace the cells lost in multiple sclerosis."
The team said that much work remains before multiple sclerosis patients might benefit from the promising approach.
Scientists still must find ways to transform the medications for internal use and determine their long-term efficacy and potential side effects.
However they said the initial findings show promise and the drugs have been shown to work on human stem cells.
“This truly represents a paradigm shift in how we think about restoring function to multiple sclerosis patients,” said Dr Robert Miller of the neurosciences faculty.
"The drugs we identified are able to enhance the regenerative capacity of stem cells in the adult nervous system. It showed a striking reversal of disease severity in the mice.”
The research was published in the journal Nature.
Source: The Daily Telegraph © Copyright of Telegraph Media Group Limited 2015 (21/04/15)
A pioneering new stem cell treatment is allowing people with multiple sclerosis to walk, run and even dance again, in results branded ‘miraculous’ by doctors.
Patients who have been wheelchair-bound for 10 years have regained the use of their legs in the groundbreaking therapy, while others who were blind can now see again.
The treatment is the first to ‘reverse’ the symptoms of MS, which has no cure, and affects around 100,000 people in Britain.
The two dozen patients who are taking part in the trials at the Royal Hallamshire Hospital in Sheffield and Kings College Hospital, London, have effectively had their immune systems ‘rebooted’.
Although it is unclear what causes MS, some doctors believe that it is the immune system itself which attacks the brain and spinal cord, leading to inflammation and pain, disability and in severe cases, death.
In the new treatment, specialists use a high dose of chemotherapy to knock out the immune system before rebuilding it with stem cells taken from the patient’s own blood.
Stem cells are so effective because they can become any cell in the body based on their environment.
"Since we started treating patients three years ago, some of the results we have seen have been miraculous," Professor Basil Sharrack, a consultant neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, told The Sunday Times.
"This is not a word I would use lightly, but we have seen profound neurological improvements."
During the treatment, the patient's stem cells are harvested and stored. Then doctors use aggressive drugs which are usually given to cancer patients to completely destroy the immune system.
The harvested stem cells are then infused back into the body where they start to grow new red and white blood cells within just two weeks.
Within a month the immune system is back up and running fully and that is when patients begin to notice that they are recovering.
Holly Drewry, 25, of Sheffield, was wheelchair bound after the birth of her daughter Isla, now two, but she claims the new treatment has transformed her life.
“It worked wonders,” she said. “I remember being in the hospital... after three weeks, I called my mum and said: 'I can stand'. We were all crying.
"I can run a little bit, I can dance. I love dancing, it is silly but I do. I enjoy walking my daughter around the park in her pram. It is a miracle but I can do it all."
However specialists warn that patients need to be fit to benefit from the new treatment.
"This is not a treatment that is suitable for everybody because it is very aggressive and patients need to be quite fit to withstand the effects of the chemotherapy," warned Prof Sharrack.
Charities welcomed the research but also urged caution.
Dr Sorrel Bickley, Research Communications Manager at the MS Society said: “This new study reports very encouraging findings, which add to a growing body of research into stem cell transplantation in MS. However, there are limitations to how we can interpret these results because there was no control group used, which means we can’t be sure the results are robust.
"Momentum in this area of research is building rapidly and we're eagerly awaiting the results of larger, randomised trials and longer term follow up data.
“New treatments for MS are urgently needed, but as yet there are no stem cell therapies licensed for MS anywhere in the world. This means they aren't yet established as being both safe and effective. This type of stem cell therapy is very aggressive and does carry significant risks, so we would strongly urge caution in seeking this treatment outside of a properly regulated clinical trial."
The research was published in the Journal of the American Medical Association.
Source: The Daily Telegraph © Copyright of Telegraph Media Group Limited 2015 (02/03/15)
Multiple sclerosis patients who had autologous hematopoietic stem-cell transplantation had significantly fewer new lesions on MRI than those on mitoxantrone, Italian researchers have found.
In a randomized, controlled trial, CD34-positive hematopoietic cell transplant reduced the number of new T2 lesions by 79 per cent compared with mitoxantrone over a four-year study period, Giovanni Mancardi, MD, of the University of Genova in Italy, and colleagues reported in Neurology.
The therapy also reduced gadolinium-enhancing lesions and annualized relapse rate, but there was no difference in progression of disability, although the study was not powered to look at the latter finding, the researchers noted.
"More research is needed with larger numbers of patients who are randomized to receive either the stem-cell transplant or an approved therapy, but it's very exciting to see that this treatment may be so superior to a current treatment for people with severe MS that are not responding well to standard treatments," Mancardi said in a statement.
The ASTIMS study enrolled 21 patients from seven centers in Italy and Spain from 2004 to 2009 who had relapsing-remitting or secondary progressive MS. They were randomized to intensive immunosuppression followed by either mitoxantrone or autologous hematopoietic stem-cell transplantation every month for 6 months.
The intensive immunosuppression regimen involved mobilization with cyclophosphamide and filgrastim, conditioning with carmustine, cytosine arabinoside, etoposide, melphalan, and anti-thymocyte globulin.
The mean age at transplantation was 35.5 years, and the median Expanded Disability Status Scale (EDSS) score at baseline was 6.
ASTIMS was designed as a phase III study, but became a phase II trial with a primary laboratory endpoint -- the cumulative number of new T2 lesions 4 years after randomization -- "when it was clear that the number of enrolled patients was lower than expected," the researchers wrote.
Overall, Mancardi and colleagues found fewer T2 lesions in the stem-cell group than in the mitoxantrone group during follow-up at a median of 2.5 lesions versus a median of eight lesions.
This effect was evident in the first year and was sustained through four years of follow-up, they reported. It was also maintained in all sensitivity analyses. It also resulted in complete suppression of active inflammatory lesions as measured by gadolinium-enhancing lesions, with no stem-cell patients having new lesions compared with 56 per cent of those on mitoxantrone.
The annualized relapse rate was also lower for stem-cell patients. However, there was no significant difference in terms of progression of disability between groups, occurring in 48 per cent of the mitoxantrone group and 57 per cent of the stem-cell group, with no differences in EDSS changes at any point, the researchers said.
Mancardi and colleagues attributed this to the study being underpowered to look for this outcome.
In addition to this limitation, and the fact that the study was changed from phase III to phase II, it was also limited by its small number of cases and by a lack of data on quality of life and brain atrophy outcomes.
In an accompanying editorial, Paolo Muraro, MD, PhD, of Imperial College London, agreed that the lack of improvement in progression of disability was likely due to the study being underpowered.
Muraro also noted that mitoxantrone might not be the contemporary choice of comparator "having lost traction because of its cardiac toxicity and risk of lymphoma," although it was the most appropriate control treatment at the time the trial was started.
Given that stem-cell transplant isn't a licensed therapy for MS, more work is needed, Muraro said, noting that a phase III trial currently underway is likely to gain traction because the current study will "raise interest and catalyse activities to move forward with the new trial."
The study was supported by the Italian Multiple Sclerosis Foundation.
Mancardi disclosed relevant relationships with Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi, and Teva. Many co-authors disclosed multiple relevant relationships with industry including Biogen Idec, Novartis, Merk-Serono, Genzyme, Teva Pharmaceutical Industries, Genmab A/S, and Bayer Schering Pharma.
Muraro disclosed no relevant relationships with industry.
Source: MedPage Today © 2015 MedPage Today, LLC (12/02/15)
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)
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)
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)
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)
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 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)
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)