A potential new treatment for multiple sclerosis lies within modified adult stem cells, University of Adelaide researchers say.
The researchers are embarking on a new project which uses stem cells from fat tissue to send cells with special anti-inflammatory properties directly to the damaged site in the central nervous system.
MS is a progressive disease where the body attacks the central nervous system, causing nerve inflammation and scarring. It results in the impairment of motor, sensory and cognitive function.
Director of the Centre for Molecular Pathology, Professor Shaun McColl, said treatments for MS need to control the immune response and repair the damage caused to the fatty myelin sheaths which protect the nerves.
"We've already shown that adult stem cells have great potential to both control the immune response and promote repair of the central nervous system. It also prevents further damage," he said.
"But the trick is getting the stem cells to the right location where they can perform this function."
When stem cells are injected into the blood system, very few cross the blood/brain barrier into the central nervous system.
Lead investigator Dr Iain Comerford said it was hoped the manipulated adult stem cells could cross that barrier, targeting the inflammation site and repairing the damaged myelin.
"It involves promoting stem cell migration to the central nervous system by manipulating receptors on the surface of the stem cells that control cell movement," Dr Comerford said.
"We're also modifying the stem cells to suppress the immune response by introducing molecules that regulate inflammation."
At the end of the three-year project, the researchers aim to show they can successfully modify the stem cells to effectively reach the central nervous system and inhibit inflammation.
"If it works, there is great potential for a new therapy for this debilitating disease," Dr Comerford said.
Source: news.com.au Copyright 2013 News Limited (10/05/13)
Scientists have discovered an antibody that can turn stem cells from a patient's bone marrow directly into brain cells, a potential breakthrough in the treatment of neurological diseases and injuries.
Richard Lerner, of the Scripps Research Institute in California, says that when a specific antibody is injected into stem cells from bone marrow—which normally turn into white blood cells—the cells can be triggered to turn into brain cells.
"There's been a lot of research activity where people would like to repair brain and spinal cord injuries," Lerner says. "With this method, you can go to a person's own stem cells and turn them into brain cells that can repair nerve injuries."
Antibodies are Y-shaped proteins that the immune system uses to help identify foreign threats to the body. They bind to foreign invaders in the body in order to alert white blood cells to attack harmful bacteria and viruses. There are millions of known antibodies.
Lerner and his team were working to find an antibody that would activate what is known as the GCSF receptor in bone marrow stem cells, in order to stimulate their growth. When they found one that worked, the researchers were surprised: Instead of inducing the stem cells to grow, they began to form into neural cells.
"The cells proliferated, but also started becoming long and thin and attaching to the bottom of the dish," which is reminiscent of behaviour of neural cells, Jia Xie, a research associate on Lerner's team, said in a released statement. Further tests confirmed that they were neural progenitor cells, which are very similar to mature brain cells.
Lerner says that scientists have "an awful lot of experience injecting antibodies" into stem cells and that the process is not "inherently dangerous." The team plans to start animal tests of the technology soon.
"We're going to collaborate with people who are trying to regenerate nerves in the eye," Lerner says. "We will team up with a couple people strong in that area of research."
Source: US News © 2013 U.S.News & World Report LP (24/04/13)
Ordinary skin cells have been directly converted into the myelinating cells destroyed in multiple sclerosis, according to two new papers in Nature Biotechnology.
Using a process they call "cellular reprogramming," researchers at Stanford University School of Medicine and Case Western Reserve School of Medicine, in two very similar papers, described how they turned the fibroblasts into what appear to be oligodendrocyte precursor cells, in mice. Oligodendrocytes produce myelin, the fatty insulation necessary to allow nerve signal conduction. It is caused by an autoimmune reaction attacking the oligodendrocytes.
" We propose direct lineage reprogramming as a viable alternative approach for the generation of OPCs for use in disease modeling and regenerative medicine," the Stanford team stated in their paper.
In multiple sclerosis, the destruction of oligodendrocytes and myelin results in symptoms such as loss of balance, problems moving arms and legs, loss of coordination and weakness, according to the National Institues of Health. Other problems include loss of bladder control, impaired vision, depression, and memory loss.
To fix these problems, not only must the autoimmune reaction be brought under control, but the myelin must be repaired. That implies producing new oligodendrocytes. Hence, the OPCs, which researchers think could become effective sources of the olgodendrocytes when transplanted. (Transplantion of fully mature cells doesn't seem to work in such studies; the cells seem to need to complete the last step of maturation in their new enviroment to wire into the nervous system.)
But until very recently, making OPCs has extremely difficult. In February, a team led by University of Rochester scientists created oligodendrocytes from induced pluripotent stem cells, which themselves were derived from fibroblasts. These cells were transplanted into animal models of multiple sclerosis, where they produced myelin.
The University of Rochester team's approach added IPS cells to other sources of oligodendrocytes, including stem cells committed to producing neural lineage-committed stem cells and embryonic stem cells. However, all of these sources require the cells to be taken through intermediate steps to get to the desired cell. By contrast, direct conversion offers a less complicated route, and avoids the troublesome pluripotent stage, in which cells are prone to form tumors.
If the Case Western or Stanford technology turns out to be useful for MS patients, it will help confirm the prediction of Ian Wilmut not long ago that direct conversion would become feasible and ultimately supplant the use of stem cells. The Case Western team spelled out this vision in their paper:
"With further optimization, this approach could provide a source of functional OPCs that will complement, and possibly obviate, the use of pluripotent stem cells and fetal cells in cell-based remyelinating therapies," the Case Western paper stated.
The induced oligodendrocyte precursor cells, or iOPCs, just produce oligodendrocytes, the paper said, while neural stem cells and induced neural stem cells are inefficient in producing them, and they produce other unwanted cells such as neurons and astrocytes.
"We have shown that iOPCs integrate into the CNS and myelinate axons of congenitally dysmyelinated mice in vivo after transplantation," the Case Western paper concluded. "However, for iOPCs to have clinical relevance, future studies will have to extend this reprogramming strategy to human somatic cells and demonstrate extensive CNS myelination and long-term functional benefit to transplant recipients."
Source: U-T San Diego © 1995-2013 The San Diego Union-Tribune, LLC (15/04/13)
A new study by multiple sclerosis researchers at three Canadian centres addresses why bone marrow transplantation (BMT) has positive results in patients with particularly aggressive forms of MS. The transplantation treatment, which is performed as part of a clinical trial and carries potentially serious risks, virtually stops all new relapsing activity as observed upon clinical examination and brain MRI scans. The study reveals how the immune system changes as a result of the transplantation. Specifically, a sub-set of T cells in the immune system known as Th17 cells, have a substantially diminished function following the treatment.
The finding to be published in the upcoming issue of Annals of Neurology and currently in the early online version, provides important insight into how and why BMT treatment works as well as how relapses may develop in MS.
"Our study examined why patients essentially stop having relapses and new brain lesions after the bone marrow transplant treatment, which involves ablative chemotherapy followed by stem cell transplantation using the patient's own cells," said Prof. Amit Bar-Or, the principle investigator of the study, who is a neurologist and MS researcher at The Montreal Neurological Institute and Hospital -The Neuro, McGill University, and Director of The Neuro's Experimental Therapeutics Program. "We discovered differences between the immune responses of these patients before and after treatment, which point to a particular type of immune response as the potential perpetrator of relapses in MS."
"Although the immune system that re-emerges in these patients from their stem cells is generally intact, we identified a selectively diminished capacity of their Th17 immune responses following therapy -- which could explain the lack of new MS disease activity. In untreated patients, these Th17 cells may be particularly important in breaching the blood-brain-barrier, which normally protects the central nervous system. This interaction of Th17 cells with the blood-brain barrier can facilitate subsequent invasion of other immune cells such as Th1 cells, which are thought to also contribute to brain cell injury.
Twenty-four patients participated in the overall clinical trial as part of the 'Canadian MS BMT' clinical trial, coordinated by Drs. Mark Freedman and Harry Atkins at the Ottawa General Hospital. The new discovery, made in a subset of patients participating in the clinical trial, was based on immunological studies carried out jointly in laboratories at The Neuro and the Université de Montréal. Results of this study not only show the clinical benefits of BMT treatment, but also open a unique window into the immunological mechanisms underlying relapses in MS. Th17 cells could be the immune cells associated with the initiation of new relapsing disease activity in this group of patients with aggressive MS. This finding deepens our understanding of MS and could guide the development of personalized medicine with a more favourable risk/benefit profile.
Among the patients treated in the Canadian MS BMT clinical trial, was Dr. Alexander Normandin, a family doctor, who was a third- year McGill medical student getting ready for his surgery exams when he first learned he had MS, "I was so engrossed in my studies that I didn't pay attention to the first sign but within a few days of waking up with a numb temple, my face felt frozen. I learned that I had a very aggressive form of MS and would probably be in a wheelchair within a year. It was a brutal blow. I became patient #19 -- of only 24 for this experimental treatment. My immune system was knocked out and then rebooted with my stem cells. Today, my MS has stabilized. I now have this disease under control and I take it one day at a time."
Both the clinical and biological studies were supported by the Research Foundation of the Multiple Sclerosis Society of Canada.
Journal Reference: Peter J. Darlington, Tarik Touil, Jean-Sebastien Doucet, Denis Gaucher, Joumana Zeidan, Dominique Gauchat, Rachel Corsini, Ho Jin Kim, Martin Duddy, Farzaneh Jalili, Nathalie Arbour, Hania Kebir, Jacqueline Chen, Douglas L. Arnold, Marjorie Bowman, Jack Antel, Alexandre Prat, Mark S. Freedman, Harold Atkins, Rafick Sekaly, Remi Cheynier, Amit Bar-Or. Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation. Annals of Neurology, 2013; DOI: 10.1002/ana.23784
Source: Science Daily Copyright © 1995-2012 ScienceDaily LLC (28/03/13)
A study out February 7 in the journal Cell Stem Cell shows that human brain cells created by reprogramming skin cells are highly effective in treating myelin disorders, a family of diseases that includes multiple sclerosis and rare childhood disorders called pediatric leukodystrophies.
The study is the first successful attempt to employ human induced pluripotent stem cells (hiPSC) to produce a population of cells that are critical to neural signaling in the brain. In this instance, the researchers utilized cells crafted from human skin and transplanted them into animal models of myelin disease.
"This study strongly supports the utility of hiPSCs as a feasible and effective source of cells to treat myelin disorders," said University of Rochester Medical Center (URMC) neurologist Steven Goldman, M.D., Ph.D., lead author of the study. "In fact, it appears that cells derived from this source are at least as effective as those created using embryonic or tissue-specific stem cells."
The discovery opens the door to potential new treatments using hiPSC-derived cells for a range of neurological diseases characterized by the loss of a specific cell population in the central nervous system called myelin. Like the insulation found on electrical wires, myelin is a fatty tissue that ensheathes the connections between nerve cells and ensures the crisp transmission of signals from one cell to another. When myelin tissue is damaged, communication between cells can be disrupted or even lost.
The most common myelin disorder is multiple sclerosis, a condition in which the body's own immune system attacks and destroys myelin. The loss of myelin is also the hallmark of a family of serious and often fatal diseases known as pediatric leukodystrophies. While individually very rare, collectively several thousand children are born in the U.S. with some form of leukodystrophy every year.
The source of the myelin cells in the brain and spinal cord is cell type called the oligodendrocyte. Oligodendrocytes are, in turn, the offspring of another cell called the oligodendrocyte progenitor cell, or OPC. Myelin disorders have long been considered a potential target for cell-based therapies. Scientists have theorized that if healthy OPCs could be successfully transplanted into the diseased or injured brain, then these cells might be able to produce new oligodendrocytes capable of restoring lost myelin, thereby reversing the damage caused by these diseases.
However, several obstacles have thwarted scientists. One of the key challenges is that OPCs are a mature cell in the central nervous system and appear late in development. "Compared to neurons, which are among the first cells formed in human development, there are more stages and many more steps required to create glial cells such as OPCs," said Goldman. "This process requires that we understand the basic biology and the normal development of these cells and then reproduce this precise sequence in the lab."
Another challenge has been identifying the ideal source of these cells. Much of the research in the field has focused on cells derived from tissue-specific and embryonic stem cells. While research using these cells has yielded critical insight into the biology of stem cells, these sources are not considered ideal to meet demand once stem cell-based therapies become more common.
The discovery in 2007 that human skin cells could be "reprogrammed" to the point where they returned to a biological state equivalent of an embryonic stem cell, called induced pluripotent stem cells, represented a new path forward for scientists. Because these cells -- created by using the recipient's own skin -- would be a genetic match, the likelihood of rejection upon transplantation is significantly diminished. These cells also promised an abundant source of material from which to fashion the cells necessary for therapies.
Goldman's team was the first to successfully master the complex process of using hiPSCs to create OPCs. This process proved time consuming. It took Goldman's lab four years to establish the exact chemical signaling required to reprogram, produce, and ultimately purify OPCs in sufficient quantities for transplantation and each preparation required almost six months to go from skin cell to a transplantable population of myelin-producing cells.
Once they succeeded in identifying and purifying OPCs from hiPSCs, they then assessed the ability of the cells to make new myelin when transplanted into mice with a hereditary leukodystrophy that rendered them genetically incapable of producing myelin.
They found that the OPCs spread throughout the brain and began to produce myelin. They observed that hiPSC-derived cells did this even more quickly, efficiently, and effectively than cells created using tissue-derived OPCs. The animals were also free of any tumors, a dangerous potential side effect of some stem cell therapies, and survived significantly longer than untreated mice.
"The new population of OPCs and oligodendrocytes was dense, abundant, and complete," said Goldman. "In fact, the re-myelination process appeared more rapid and efficient than with other cell sources."
The next stage in evaluating these cells -- clinical studies -- may not be long in the offing. Goldman, along with a team of researchers and clinicians from Rochester, Syracuse, and Buffalo, are preparing to launch a clinical trial using OPCs to treat multiple sclerosis. This group, titled the Upstate MS Consortium, has been approved for funding by New York State Stem Cell Science (NYSTEM). While the consortia's initial study -- the early stages of which are scheduled to begin in 2015 -- will focus cells derived from tissue sources, Goldman anticipates that hiPSC-derived OPCs will eventually be included in this project.
Source: ScienceDaily Copyright © 1995-2012 ScienceDaily LLC (08/02/13)
Scientists in recent years have found a way to infuse stem cells into the brains of animals to repair damage to the central nervous system, offering some of the most encouraging news yet for multiple sclerosis patients.
Now, a key $12.1 million study soon will be under way in Buffalo and two other upstate medical centers that will for the first time begin to test the procedure in people.
The hope is that the stem cells will generate new myelin, the fatty substance that surrounds nerves like the insulation on a wire. Myelin is damaged in MS, leading to weak or lost signals between nerves. Eventually, the painful disease spreads in a slow, unpredictable path toward paralysis.
“This is a promising strategy. It has been extraordinarily effective in mice, and there is great hope the technique will be successful in people,” said Dr. Steven Goldman, co-principal investigator and co-director of the University of Rochester Center for Translational Neuromedicine.
The study by researchers in Rochester, the University at Buffalo and Upstate Medical University in Syracuse has far-ranging implications. It potentially could be applied to millions of patients with a host of other conditions, including Alzheimer’s and Parkinson’s disease.
Although stem cells show great promise, the approach is a ways from reality.
What works in mice does not always work in humans. In addition, scientists don’t know what causes MS, so they can’t exactly replicate MS in animals, complicating tests of the potential new treatment.
“Expectations have to be kept under control. You’re not going to implant stem cells in people and suddenly see them running around,” said Dr. Bianca Guttman-Weinstock, co-principal investigator at UB.
Stem cells are often referred to as master cells because they develop into the many different types of cells in the body that form organs and tissue. Stem cells also have the potential to repair or replace damaged cells.
Other scientists are looking at whether it may be possible to use certain stem cells to prevent the body’s immune system from attacking nerves.
“There is a lot happening in stem cell research, and it’s exciting because five years ago, these were just ideas. Now, they are reality,” said Dr. Timothy Coetzee, chief research officer at the National MS Society.
Until recently, scientists didn’t know exactly which master stem cells ultimately developed into cells that make myelin in a complicated process. They now know that cells called oligodendrocytes produce myelin. They also learned how to turn stem cells into a type of cell called glial progenitor cells. Glial progenitor cells are the cells that make oligodendrocytes.
These findings allowed scientists to transplant oligodendrocytes into the brains of mice that had no myelin. The result: The cells began to repair damaged areas.
“It was an extraordinarily effective strategy,” said Goldman.
All this progress has occurred in the last few years, including a study published late last year using stem cells transplanted into the brains of children with a rare genetic brain disease known as Pelizaeus-Merzbacher disease, in which myelin is lacking.
The significance of the research is that it indicates stem cells can be safely transplanted and may be effective at making myelin.
Children are different than adults, but Goldman and others say there is great hope the technique will succeed in adults.
The first step
The upstate consortium study for MS, which is funded by the Empire State Stem Cell Board, is the first step in a typical research process, which occurs in phases and usually takes many years to complete.
In the first two phases, scientists test the safety and effectiveness of an experimental treatment, and that’s what will happen with this stem cell trial for MS.
Patients enrolled in the study will be those with secondary progressive MS. These individuals no longer have periods of remission and, instead, experience a slow but steady worsening of symptoms with no approved therapy. Small holes will be drilled into their skulls and stem cells injected through catheters inserted in the holes.
The original proposal for the study recommended obtaining stem cells from discarded fetal brains. Technology has progressed enough that the current plan, dependent on government approval, is to start with stem cells from the patient’s own skin cells and reprogram them into cells useful for making myelin.
Before the first patients can receive the treatment in 2016, researchers must spend the next few years preparing for the trial. Among other things, they need to refine how they will measure the repair of myelin, as well as improvements in the patients. It’s a tricky issue because improvements are likely to occur slowly and will vary from person to person, said Guttman-Weinstock.
A key role
It seems fitting that the study will include Buffalo.
Research by the late Dr. Lawrence D. Jacobs, a Buffalo neurologist, played a key role in the development of Avonex, the drug most widely prescribed to treat relapsing MS.
Population studies show that higher rates of MS exist in temperate climates, in particular a geographic band in North America across the northern United States and southern Canada that includes Western New York.
If stem cells work, it could change the lives of millions of people worldwide who suffer from a disease that can be unbearable as patients decline in function and health.
That’s why many individuals like Shelly Boyle track research on potential MS treatments with a laser-like focus.
“I read everything I can read,” said Boyle, a 48-year-old Cheektowaga resident who was diagnosed with MS in 1990.
She stopped working as a chiropractor in 2004 as her symptoms worsened. She has trouble walking and coordinating the small muscles in her fingers. The medication she has been taking is no longer effective.
“The idea of drilling into my brain would scare me if I was in the trial, but the prospect of something new on the horizon is exciting,” she said. “I’m running out of options.”
Source: The Buffalo News Copyright 1999 - 2013 - The Buffalo News (14/01/13)
In a new study appearing this month in the Journal of Neuroscience, researchers have unlocked the complex cellular mechanics that instruct specific brain cells to continue to divide. This discovery overcomes a significant technical hurdle to potential human stem cell therapies; ensuring that an abundant supply of cells is available to study and ultimately treat people with diseases.
"One of the major factors that will determine the viability of stem cell therapies is access to a safe and reliable supply of cells," said University of Rochester Medical Center (URMC) neurologist Steve Goldman, M.D., Ph.D., lead author of the study.
"This study demonstrates that – in the case of certain populations of brain cells – we now understand the cell biology and the mechanisms necessary to control cell division and generate an almost endless supply of cells."
The study focuses on cells called glial progenitor cells (GPCs) that are found in the white matter of the human brain. These stem cells give rise to two cells found in the central nervous system: oligodendrocytes, which produce myelin, the fatty tissue that insulates the connections between cells; and astrocytes, cells that are critical to the health and signaling function of oligodendrocytes as well as neurons. Damage to myelin lies at the root of a long list of diseases, such as multiple sclerosis, cerebral palsy, and a family of deadly childhood diseases called pediatric leukodystrophies. The scientific community believes that regenerative medicine – in the form of cell transplantation – holds great promise for treating myelin disorders.
Goldman and his colleagues, for example, have demonstrated in numerous animal model studies that transplanted GPCs can proliferate in the brain and repair damaged myelin. However, one of the barriers to moving forward with human treatments for myelin disease has been the difficulty of creating a plentiful supply of necessary cells, in this case GPCs. Scientists have been successful at getting these cells to divide and multiply in the lab, but only for limited periods of time, resulting in the generation of limited numbers of usable cells.
"After a period of time, the cells stop dividing or, more typically, begin to specialize and form astrocytes which are not useful for myelin repair," said Goldman. "These cells could go either way but they essentially choose the wrong direction."
Overcoming this problem required that Goldman's lab master the precise chemical symphony that occurs within stem cells, and which instructs them when to divide and multiply, and when to stop this process and become oligodendrocytes and astrocytes. One of the key players in cell division is a protein called beta-catenin. Beta-catenin is regulated by another protein in the cell called glycogen synthase kinase 3 beta (GSK3B). GSK3B is responsible for altering beta-catenin by adding an additional phosphate molecule to its structure, essentially giving it a barcode that the cell then uses to sort the protein and send it off to be destroyed. During development, when cell division is necessary, this process is interrupted by another signal that blocks GSK3B. When this occurs, the beta-catenin protein is spared destruction and eventually makes its way to the cell's nucleus where it starts a chemical chain reaction that ultimately instructs the cell to divide.
However, after a period of time this process slows and, instead of replicating, the cells begin to then commit to becoming one type or another.
The challenge for scientists was to find another way to essentially trick these cells into continuing to divide, and to do so without risking the uncontrolled growth that could otherwise result in tumor formation.
The new discovery hinges on a receptor called protein tyrosine phosphatase beta/zeta (PTPRZ1). Goldman and his team long suspected that PTPRZ1 played an important role in cell division; the receptor shows up prominently in molecular profiles of GPCs. After a six-year effort to discern the receptor's function, they found that it works in concert with GSK3B and helps "label" beta-catenin protein for either destruction or nuclear activity. The breakthrough was the identification of a molecule – called pleiotrophin – that essentially blocks the function of the PTPRZ1 receptor. They found that by regulating the levels of pleiotrophin, they were able to essentially "short circuit" PTPRZ1's normal influence on cell division, allowing the cells to continue dividing.
While the experiments were performed on cells derived from human brain tissue, the authors contend that the same process could also be applied to GPCs derived from embryos or from "reprogrammed" skin cells. This would greatly expand the number of cells potentially derived from single patient samples, whether for transplantation back to those same individuals or for use in other patients.
Source: Medical Xpress © Medical Xpress 2011-2012 (01/11/12)
When the era of regenerative medicine dawned more than three decades ago, the potential to replenish populations of cells destroyed by disease was seen by many as the next medical revolution. However, what followed turned out not to be a sprint to the clinic, but rather a long tedious slog carried out in labs across the globe required to master the complexity of stem cells and then pair their capabilities and attributes with specific diseases.
In a review article appearing in the journal Science, University of Rochester Medical Center scientists Steve Goldman, M.D., Ph.D., Maiken Nedergaard, Ph.D., and Martha Windrem, Ph.D., contend that researchers are now on the threshold of human application of stem cell therapies for a class of neurological diseases known as myelin disorders - a long list of diseases that include conditions such as multiple sclerosis, white matter stroke, cerebral palsy, certain dementias, and rare but fatal childhood disorders called pediatric leukodystrophies.
"Stem cell biology has progressed in many ways over the last decade, and many potential opportunities for clinical translation have arisen," said Goldman. "In particular, for diseases of the central nervous system, which have proven difficult to treat because of the brain's great cellular complexity, we postulated that the simplest cell types might provide us the best opportunities for cell therapy."
The common factor in myelin disorders is a cell called the oligodendrocyte. These cells arise, or are created, by another cell found in the central nervous system called the glial progenitor cell. Both oligodendrocytes and their "sister cells" - called astrocytes - share this same parent and serve critical support functions in the central nervous systems.
Oligodendrocytes produce myelin, a fatty substance that insulates the fibrous connections between nerve cells that are responsible for transmitting signals throughout the body. When myelin-producing cells are lost or damaged in conditions such as multiple sclerosis and spinal cord injury, signals traveling between nerves are weakened or even lost. Astrocytes also play an essential role in the brain. Long overlooked and underappreciated, it is now understood that astrocytes are critical to the health and signaling function of oligodendrocytes as well as neurons.
Glial progenitor cells and their offspring represent a promising target for stem cell therapies, because - unlike other cells in the central nervous system - they are relatively homogeneous and more readily manipulated and transplanted. In the case of oligodendrocytes, multiple animal studies have shown that, once transplanted, these cells will disperse and begin to repair or "remyelinate" damaged areas.
"Glial cell dysfunction accounts for a broad spectrum of diseases, some of which - like the white matter degeneration of aging - are far more prevalent than we previously realized," said Goldman. "Yet glial progenitor cells are relatively easy to work with, especially since we don't have to worry about re-establishing precise point to point connections as we must with neurons. This gives us hope that we may begin to treat diseases of glia by direct transplantation of competent progenitor cells."
Scientists have reached this point, according to the authors, because of a number of key advances. Better imaging technologies - namely advanced MRI scanners - now provide greater insight and clarity into the specific damage caused in the central nervous system by myelin disorders. These technologies also enable scientists to precisely follow the results of their work.
Even more importantly, researchers have overcome numerous obstacles and made significant strides in their ability to manipulate and handle these cells. Goldman's lab in particular has been a pioneer in understanding the precise chemical signals necessary to coax stem cells into making glial progenitor cells, as well as those needed to "instruct" these cells to make oligodendrocytes or astrocytes. His lab has been able to produce these cells from a number of different sources - including "reprogramming" skin cells, a technology that has the advantage of genetically matching transplanted cells to the donor. They have also developed techniques to sort these cells based on unique identifying markers, a critical step that ensures the purity of the cells used in transplantation, lowering the risk for tumor formation.
Nedergaard's lab has studied the integration of these cells into existing neural networks, and well as in imaging their structure and function in the adult nervous system. Together, the two labs have developed models of both human neural activity and disease based on animals transplanted with glial progenitor cells, which will enable human neural cells to be evaluated in the context of the live adult brain - as opposed to a test tube. This work has already opened new avenues in both modeling and potentially treating human glial disease.
All of these advances, contend the authors, have accelerated research to the point where human studies for myelin disorders are close at hand. For instance, diseases such as multiple sclerosis, which benefit from a new generation of stabilizing anti-inflammatory drugs, may be an especially appealing target for progenitor-based cell therapies which could repair the now permanent and untreatable damage to the central nervous system that occurs in the disease. Similarly, the authors point to a number of the childhood diseases of white matter that now appear ripe for cell-based treatment.
"We have developed a tremendous amount of information about these cells and how to produce them," said Goldman. "We understand the different cell populations, their genetic profiles, and how they behave in culture and in a variety of animal models. We also have better understanding of the disease target environments than ever before, and have the radiographic technologies to follow how patients do after transplantation. Moving into clinical trials for myelin disorders is really just a question of resources at this point."
Source: Medical News Today © MediLexicon International Ltd 2004-2012 (29/10/12)
New research suggests that stem cell transplants to treat certain brain and nervous system diseases such as multiple sclerosis may be moving closer to reality.
One study found that experimental stem cell transplants are safe and possibly effective in children with a rare genetic brain disease. Another study in mice showed that these cells are capable of transforming into, and functioning as, the healthy cell type. The stem cells used in the two studies were developed by study sponsor StemCells, Inc.
Both papers appear online in Science Translational Research.
The work, while still in its infancy, may have far-reaching implications for the treatment of many more common diseases that affect the brain and nervous system.
Researchers out of the University of California, San Francisco (UCSF), looked at the how neural stem cells behaved when transplanted into the brains of four young children with an early-onset, fatal form of Pelizaeus-Merzbacher disease (PMD).
Can Stem Cell Transplants Help Treat MS?
PMD is a very rare genetic disorder in which brain cells called oligodendrocytes can’t make myelin. Myelin is a fatty substance that insulates the nerve fibers of the brain, spinal cord, and optic nerves (central nervous system), and is essential for transmission of nerve signals so that the nervous system can function properly.
In multiple sclerosis, the myelin surrounding the nerve is targeted and damaged by the body’s immune system.
The new study found that the neural stem cell transplants were safe. What’s more, brain scans showed that the implanted cells seem to be doing what is expected of them -- i.e. making myelin.
Researchers compared treated areas of participants' brains with untreated areas. "The study goes beyond safety and we see some effects in the transplanted region that are consistent with the appearance of myelin, at one year,” says study author David H. Rowitch, MD, PhD. “It is not definitive, but it is suggestive.” He is a professor of pediatrics and neurological surgery at UCSF, and is the chief of neonatology at UCSF Benioff Children’s Hospital.
PMD is rare, but other diseases that affect the myelin, such as MS, are more common.
So is it possible that these same stem cell transplants could also benefit these other diseases? Although the possibility exists, Rowitch is noncommittal at this point. “We don’t have data that this could work in MS or other diseases,” he says.
With PMD, the cells that produce myelin are not doing their job. Other diseases involve multiple causes or pathways. If further research in treating PMD pans out, the next step will be to look at MS and other diseases that affect myelin, Rowitch says.
Nancy L. Sicotte, MD, is the director of the Multiple Sclerosis Program at Cedars-Sinai Medical Center in Los Angeles. She says that MS may be more complicated to treat with stem cell therapy.
“With MS, we would be trying to introduce stem cells into an inflamed nervous system,” she says. "To be effective, we have to stop the inflammation process, which we haven’t fully been able to do yet.”
Still, “stem-cell based therapies hold a lot of promise and potential,” Sicotte says. “You always have to temper that with the fact that it takes time to bring a great idea in the lab to humans.”
A Big Deal
A related study by researchers at Oregon Health & Science University's (OHSU) Doernbecher Children’s Hospital in Portland showed that banked brain stem cells can survive and make myelin in mice with symptoms of myelin loss. This work served as one of the building blocks for the study in children with PMD.
This mouse study also gives scientists a glimpse into how these cells behave once they are transplanted, says researcher Stephen A. Back, MD, PhD. He is a clinician-scientist in the Papé Family Pediatric Research Institute at OHSU Doernbecher. “When implanted, they preferentially make myelin-forming cell.”
This is a big deal.
“Stem cells are capable of making new myelin in a brain showing deterioration, and that is very exciting,” he says. “We were surprised to see how well the new myelin was able to form in symptomatic animals.”
The implications are far-reaching. For example, “if we show in a rare disorder like PMD that patients benefit from the transplants, then we will want to do newborn screening to pick up babies with the disorders and get them transplanted as soon as possible,” Back says. “The sooner you get to these kids, the better, [since] the disease can progress like gangbusters once it starts.”
Source: WebMD ©2005-2012 WebMD, LLC. (11/10/12)
Athersys, Inc. announced today it is presenting new research results at the Second Midwest Conference on Stem Cell Biology & Therapy at Oakland University in Rochester, Michigan, that highlight the potential for MultiStem®, its proprietary adult stem cell therapy, to treat multiple sclerosis (MS).
The work conducted by Athersys scientists, in collaboration with Robert Miller, Ph.D. and other scientists from Case Western Reserve University School of Medicine, and with the support of Fast Forward, a subsidiary of the National Multiple Sclerosis Society, demonstrates the potential benefits of MultiStem therapy for treating MS. In standard preclinical models of MS, researchers observed that MultiStem administration results in sustained behavioral improvements, arrests the demyelination process that is central to the pathology of MS, and supports remyelination of affected axons.
"MultiStem therapy has shown promise in treating multiple disease indications in the neurological and inflammatory and immune disease areas," said Robert Mays, Ph.D., Head of Neuroscience at Athersys. "Multiple sclerosis presents as a neurological disorder, but a central component underlying the disease is immune system dysfunction. The results of our latest preclinical studies confirm that the immunomodulatory and regenerative properties of MultiStem therapy could have relevance for treatment of this disease."
In preclinical experiments, rodents were given either an intravenous injection of MultiStem cells or placebo after the onset of symptoms in an MS model. The rodents treated with MultiStem displayed sustained and statistically significant improvement in functional testing compared to placebo treated animals. This functional improvement correlated with a statistical decrease in demyelinated lesions in the nervous system of cell treated animals compared to placebo as well as increased remyelination in cell treated animals, and this result has been confirmed in a second animal model of MS, suggesting that MultiStem treatment may accelerate the process of axonal remyelination.
"Long-term successful treatment of demyelinating diseases, such as MS, will likely require both the regulation of the immune system and the promotion of remyelination to protect axonal integrity," said Robert Miller, Ph.D., Vice President for Research and Technology Management at Case Western Reserve University. Miller also serves as Director of the Center for Translational Neuroscience at the university's School of Medicine. "I am pleased that the most recent studies suggest that MultiStem treatment influences both aspects of the disease, which means it has great potential as an attractive therapeutic option."
In 2011, Athersys and Fast Forward, LLC, a nonprofit subsidiary of the National Multiple Sclerosis Society, announced an alliance to fund the development of MultiStem for the treatment of MS, including treatment of chronic progressive forms of the disease. Fast Forward committed up to $640,000 to fund the advancement of the program to the clinical development stage.
MS is a chronic, unpredictable neurological disease that affects the central nervous system. It is thought to be an autoimmune disorder, meaning the immune system incorrectly attacks healthy tissue. Symptoms may be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision. These problems may be permanent or may come and go. According to the National MS Society, at least 400,000 Americans have MS, and every hour someone is newly diagnosed. MS affects about 2.5 million people worldwide.
MultiStem® cell therapy is a patented product that has shown the ability to promote tissue repair and healing in a variety of ways, such as through the production of multiple therapeutic factors produced in response to signals of inflammation and tissue damage. MultiStem has demonstrated therapeutic potential for the treatment of inflammatory and immune disorders, neurological conditions, and cardiovascular disease, as well as other areas, and represents a unique "off-the-shelf" stem cell product that can be manufactured in a scalable manner, may be stored for years in frozen form, and is administered without tissue matching or the need for immune suppression. The product is extensively characterized for safety, consistency and potency. Athersys has forged strategic partnerships with Pfizer Inc. to develop MultiStem for inflammatory bowel disease and with RTI Biologics, Inc. to develop cell therapy for use with a bone allograft product in the orthopedic market.
Athersys is a clinical stage biotechnology company engaged in the discovery and development of therapeutic product candidates designed to extend and enhance the quality of human life. The Company is developing its MultiStem® cell therapy product, a patented, adult-derived "off-the-shelf" stem cell product platform for disease indications in the cardiovascular, neurological, inflammatory and immune disease areas. The Company currently has several clinical stage programs involving MultiStem, including for treating inflammatory bowel disease, ischemic stroke, damage caused by myocardial infarction, and for the prevention of graft versus host disease. Athersys has also developed a diverse portfolio that includes other technologies and product development opportunities, and has forged strategic partnerships and collaborations with leading pharmaceutical and biotechnology companies, as well as world-renowned research institutions in the United States and Europe to further develop its platform and products.
About Fast Forward, LLC
Fast Forward, LLC is a nonprofit organization established by the National Multiple Sclerosis Society in order to accelerate the development of treatments for MS. Fast Forward accomplishes its mission by connecting university-based MS research with private-sector drug development and by funding small biotechnology/pharmaceutical companies to develop innovative new MS therapies and repurpose FDA-approved drugs as new treatments for MS.
Source: Athersys, Inc. (05/10/12)
One of the most promising and exciting treatment avenues for multiple sclerosis is the use of a patient's own stem cells to try to stop -- or even repair -- some of the disease's brain tissue damage.
But injecting a patient with a dose of his or her own bone-marrow stem cells was actually a pretty crude method of treating the disease, because no one was quite sure how or why it worked. Last year, doctors at the Cleveland Clinic, University Hospitals Seidman Cancer Center and Case Western Reserve University began trying this for MS patients in a Phase 1 clinical trial after positive results were seen in mice.
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.
Like many other researchers using stem cells, the local group didn't know exactly how their treatment worked, but they knew that when they gave these human mesenchymal stem cells, or MSCs, to mice with a mouse version of the disease, the mice got better.
Figuring out why the mice improved could help researchers see if the MSC injection will work well in a particular patient before the patient is injected, and possibly augment or improve the treatment as well.
In May, the research group at CWRU, headed up by neurosciences professor Robert Miller, discovered exactly what it is in the stem-cell soup that has a healing effect: a large molecule called hepatocyte growth factor, or HGF. The team published their results in Nature Neuroscience.
Miller's group knew that it could be the stem cells themselves, by coming in physical contact with the myelin damage, that were having a healing effect. Or it could be something the stem cells secreted into the surrounding liquid culture, or media, they were grown in, that was key. HGF is secreted by the stem cells, Miller said.
The team identified the HGF by first injecting only the liquid the stem cells were grown in, but not the stem cells themselves, into the mice they were studying. The mice got better, so the team knew whatever was helping was in the media.
Next, they isolated the small, medium and large molecules from the media and tried each size on the mice. Only the large-molecule treatment had the healing effect, meaning that whatever was helping was somewhere in that mix, Miller said.
"The molecule that jumped out at us was HGF," he said, because it is the right size, is made by MSCs, and in a couple of studies had been shown to be involved in myelin repair.
So the scientists took a purified sample of HGF and injected it into the sick mice. They got better. When they blocked the receptor for HGF in the mice, they stayed sick. It was pretty compelling evidence that they'd found what they'd been looking for, Miller said.
"We went on to show that HGF, like the MSCs, is regulating both the immune response, and it is independently promoting myelin repair in the brain," he said.
MSCs, taken from the bone marrow, are currently being tested in more than 150 clinical trials in the United States and around the world to treat conditions such as osteoarthritis, diabetes, emphysema and stroke.
The local Phase 1 trial has enrolled 16 of 24 total patients, and eight of them have completed the trial protocol, said Dr. Jeffrey Cohen, Cleveland Clinic neurologist and lead investigator of the trial.
So far, the treatment seems to be working, Cohen said.
"It's a little early to be saying it, but things have looked encouraging."
And there have been no safety concerns and almost no side effects. There has also been no activation -- an aggravation or return of symptoms -- of this relapsing disease in the patients involved, which has happened unexpectedly with other types of MS treatments.
Miller's discovery won't change the course of the trial currently under way at the Clinic and UH, but it may change the future of MSC treatment.
While they don't know yet what the outcome of that trial will be, it's possible that if a patient doesn't respond to the treatment, it could mean that his stem cells aren't producing enough HGF to be effective at healing, Miller said. Miller will be studying MSC samples from all the patients in the trial to find out if those who are better at producing HGF fare better.
He'll also be trying to see if they can predict how well a patient will do based on his HGF levels in the MSC sample.
"Finally, though we're a long way from this, maybe we could augment the expression of HGF in patients whose stem cells aren't that effective to enhance their effectiveness," he said.
But why not just inject the HGF alone? Miller said there are two reasons. First, the receptor for HGF in the cells, called c-MET, has been implicated in liver and breast cancer. Injecting HGF by itself into the body may stimulate the c-MET pathway, he said, and the research team is not willing to risk that.
"The stem cells have the advantage that they tend to home to the area of insult, so they don't stick around in other parts of the body," he said. "They target the treatment where it's needed."
Miller said his group is experimenting with a way of delivering HGF directly into the area of injury in the brain to minimize its contact with the rest of the body. HGF and c-MET are not associated with brain tumors.
They are also trying to test small fragments of the growth factor as a treatment, to see if they can eliminate some of the cancer concerns.
Cohen's group hopes to have results from the Phase 1 trial available in the spring and has already started planning a larger study based on those results.
Source: North East Ohio © 2012 Cleveland Live LLC (05/09/12)
The Myelin Repair Foundation (MRF) today announced the achievement of a myelin repair Phase 1 clinical trial for multiple sclerosis earlier than the foundation's goal set for 2014. By establishing its Accelerated Research Collaboration (ARC) Model to advance myelin repair treatments forward into clinical trial Phase 1 within a decade, the Myelin Repair Foundation achieved this critical milestone ahead of its goal, validating the efficiency of the ARC model to speed drug development.
This Phase 1 clinical trial conducted at Cleveland Clinic will examine the efficacy of a new myelin repair therapeutic pathway with mesenchymal stem cells (MSCs), based on MRF supported research conducted by MRF Principal Investigator Dr. Robert Miller, Professor of Neurosciences and Vice President for Research & Technology Management at Case Western Reserve University. To date, half of the 24 patients planned for this initial trial have been enrolled.
"Scientists hope that one day their research will reach clinical trials, and I'm thrilled to achieve this milestone in my career," said Dr. Robert Miller. "Without the support of Myelin Repair Foundation funding a critical component of our research that is the basis of this trial, this achievement would not have been possible. Our partnership with the Myelin Repair Foundation has helped identify new pathways to treat disease that reverses damage, ultimately accomplishing so much more than the suppression of MS symptoms."
Funded by the Myelin Repair Foundation, Dr. Miller's team of scientists identified an innovative clinical pathway through mesenchymal stem cell signals that not only protect myelin, which is damaged by the autoimmune reaction in MS, but also facilitates myelin repair. Current MS drugs on the market only focus on the suppression of the immune system to protect myelin from future damage; patients have no treatment options available to repair myelin once damage occurs in MS.
"Our goal to support research that would enter Phase 1 trials within a decade was deemed nearly impossible," said Scott Johnson, president and CEO of the Myelin Repair Foundation. "To think we achieved this ambitious goal even earlier than we planned illustrates the effectiveness of our innovative research model that accelerates promising scientific discoveries into clinical trials. Even with this success, we refuse to rest on our laurels and will continue to progress myelin research into multiple clinical trials. We remain focused on our singular goal: To speed the development of an effective myelin repair treatment to reach patients with multiple sclerosis."
About the Myelin Repair Foundation
The Myelin Repair Foundation (MRF) is a Silicon Valley-based, non-profit research organization focused on accelerating the discovery and development of myelin repair therapeutics for multiple sclerosis. Its Accelerated Research Collaboration(TM) (ARC(TM)) model is designed to optimize the entire process of medical research, drug development and the delivery of patient treatments.
Source: MarketWatch Copyright © 2012 MarketWatch, Inc (15/06/12)
A UC Irvine immunologist will receive $4.8 million to create a new line of neural stem cells that can be used to treat multiple sclerosis.
The California Institute for Regenerative Medicine awarded the grant Thursday, May 24, to Thomas Lane of the Sue & Bill Gross Stem Cell Research Center at UCI to support early-stage translational research.
CIRM's governing board gave 21 such grants worth $69 million to 11 institutions statewide. The funded projects are considered critical to the institute's mission of translating basic stem cell discoveries into clinical cures. They are expected to either result in candidate drugs or cell therapies or make significant strides toward such treatments, which can then be developed for submission to the Food & Drug Administration for clinical trial.
Lane's grant brings total CIRM funding for UCI to $76.65 million.
"I am delighted that CIRM has chosen to support our efforts to advance a novel stem cell-based therapy for multiple sclerosis," said Peter Donovan, director of the Sue & Bill Gross Stem Cell Research Center.
MS is a disease of the central nervous system caused by inflammation and loss of myelin, a fatty tissue that insulates and protects nerve cells. Current treatments are often unable to stop the progression of neurologic disability - most likely due to irreversible nerve destruction resulting from myelin deficiencies. The limited ability of the body to repair damaged nerve tissue highlights a critically important and unmet need for MS patients.
In addressing this issue, Lane - who also directs UCI's Multiple Sclerosis Research Center - will target a stem cell treatment that will not only halt ongoing myelin loss but also encourage the growth of new myelin that can mend damaged nerves.
"Our preliminary data are very promising and suggest that this goal is possible," said Lane, a Chancellor's Fellow and professor of molecular biology & biochemistry. "Research efforts will concentrate on refining techniques for production and rigorous quality control of transplantable cells generated from high-quality human pluripotent stem cell lines, leading to the development of the most therapeutically beneficial cell type for eventual use in patients with MS."
The best estimates indicate that there are 400,000 people diagnosed with MS in the U.S., with nearly half - about 160,000 - living in California. The economic, social and medical costs associated with the disease are in the billions of dollars, placing a significant burden on the state's healthcare system.
As an MS patient and research advocate, Nan Luke sees support for Lane's work as a positive step toward a regenerative therapy. The Irvine attorney was diagnosed with MS more than 20 years ago, and current treatments have slowed its progress but cannot undo damage to critical areas of her brain.
"This new research gives me and others like me real hope that our nerve damage may be repaired and that we may regain lost function," said Luke, who serves on the Sue & Bill Gross Stem Cell Research Center's patient advocacy committee.
Lane will collaborate with Australian MS researcher Claude Bernard at Monash University in Melbourne, who will help validate the cell line's effectiveness. Australia's National Health & Medical Research Council will provide a supplemental $1.8 million as part of CIRM's new collaborative funding program.
Additionally, Jeanne Loring, director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla, will work with Lane to develop the neural stem cells to be used in the study.
Source: NewsMedical.net (28/05/12)
A substance in human mesenchymal stem cells that promotes growth appears to spur restoration of nerves and their function in rodent models of multiple sclerosis (MS), researchers at Case Western Reserve University School of Medicine have found.
Their study appeared in the online version of Nature Neuroscience on Sunday, May 20.
In animals injected with hepatocyte growth factor, inflammation declined and neural cells grew. Perhaps most important, the myelin sheath, which protects nerves and their ability to gather and send information, regrew, covering lesions caused by the disease.
"The importance of this work is we think we've identified the driver of the recovery," said Robert H. Miller, professor of neurosciences at the School of Medicine and vice president for research at Case Western Reserve University.
Miller, neurosciences instructor Lianhua Bai and biology professor Arnold I. Caplan, designed the study. They worked with Project Manager Anne DeChant, and research assistants Jordan Hecker, Janet Kranso and Anita Zaremba, from the School of Medicine; and Donald P. Lennon, a research assistant from the university's Skeletal Research Center.
In MS, the immune system attacks myelin, risking injury to exposed nerves' intricate wiring. When damaged, nerve signals can be interrupted, causing loss of balance and coordination, cognitive ability and other functions. Over time, intermittent losses may become permanent.
Miller and Caplan reported in 2009 that when they injected human mesenchymal stem cells into rodent models of MS, the animals recovered from the damage wrought by the disease. Based on their work, a clinical trial is underway in which MS patients are injected with their own stem cells.
In this study, the researchers first wanted to test whether the presence of stem cells or something cells produce promotes recovery. They injected mice with the medium in which mesenchymal stem cells, culled from bone marrow, grew.
All 11 animals, which have a version of MS, showed a rapid reduction in functional deficits.
Analysis showed that the disease remained on course unless the molecules injected were of a certain size; that is, the molecular weight ranged between 50 and 100 kiloDaltons.
Research by others and results of their own work indicated hepatocyte growth factor, which is secreted by mesenchymal stem cells, was a likely instigator.
The scientists injected animals with 50 or 100 nanograms of the growth factor every other day for five days. The level of signaling molecules that promote inflammation decreased while the level of signaling molecules that counter inflammation increased. Neural cells grew and nerves laid bare by MS were rewrapped with myelin. The 100-nanogram injections appeared to provide slightly better recovery.
To test the system further, researchers tied up cell-surface receptors, in this case cMet receptors that are known to work with the growth factor.
When they jammed the receptors with a function-blocking cMet antibody, neither the mesenchymal stem cell medium nor the hepatocyte growth factor injections had any effect on the disease. In another test, injections of an anti-hepatocyte growth factor also blocked recovery.
The researchers will continue their studies, to determine if they can screen mesenchymal stem cells for those that produce the higher amounts of hepatocyte growth factor needed for effective treatment. That could lead to a more precise cell therapy.
"Could we now take away the mesenchymal stem cells and treat only with hepatocyte growth factor?" Miller asked. "We've shown we can do that in an animal but it's not clear if we can do that in a patient."
They also plan to test whether other factors may be used to stimulate the cMet receptors and induce recovery.
Source: Medical Xpress © Medical Xpress 2011-2012 (21/05/12)
The Myelin Repair Foundation (MRF) today announced the results of a new peer-reviewed research study published in Nature Neuroscience that demonstrates functional improvement in immune response modulation and myelin repair with factors derived from mesenchymal stem cell (MSC) treatment in animal models of multiple sclerosis (MS).
Funded by the Myelin Repair Foundation, this research conducted by Case Western Reserve University scientists showed positive results with human mesenchymal stem cells in animal models of MS by not only successfully blocking the autoimmune MS response, but also repairing myelin, demonstrating an innovative potential myelin repair treatment for MS.
Multiple sclerosis is a disease of the immune system that attacks the myelin, causing exposed nerves or "lesions" which block brain signals, causing loss of motor skills, coordination and cognitive ability. Compared to the controls, this research study showed fewer and smaller lesions found on the nerves in the MSC treatment group. MSCs were found to block the formation of scar tissue by suppressing the autoimmune response, which would otherwise cause permanent damage to the nerves. Furthermore, the research showed that MSC treatment also repaired myelin, enhancing myelin regeneration of the damaged axon and the rewrapping of the myelin around the axon in animal models of MS. One treatment of MSCs provided long-term protection of the recurring disease.
Led by Myelin Repair Foundation Principal Investigator and Vice President for Research & Technology Management at Case Western Reserve University's Dr. Robert Miller, this study documents a new promising pathway for treating multiple sclerosis that blocks the autoimmune response and reverses the myelin damage in animal models of MS. The human MSCs used in this study were culled from adult stem cells derived from the bone marrow.
"We are thrilled with the publication of this important research study that examines a new pathway to treat multiple sclerosis, one that reverses the damage of the disease," said Dr. Robert Miller. "Since we were just beginning to understand how MSCs provide myelin repair for lesions, with the Myelin Repair Foundation's support, we continue to deepen our knowledge of exploring the next generation of MS treatments that stimulate healing, rather than symptom suppression of the disease."
"We pride ourselves on supporting best-in-class scientists devoted to find new ways to treat multiple sclerosis, advancing highly innovative research projects that otherwise would not have moved forward," said Scott Johnson, president of the Myelin Repair Foundation. "The success of Case Western Reserve University's study and recognition in this prestigious journal furthers our goal to identify new pathways to treat multiple sclerosis by supporting a multi-disciplinary team of the best researchers in the field."
About the Myelin Repair Foundation
The Myelin Repair Foundation (MRF) is a Silicon Valley-based, non-profit research organization focused on accelerating the discovery and development of myelin repair therapeutics for multiple sclerosis. Its Accelerated Research Collaboration(TM) (ARC(TM)) model is designed to optimize the entire process of medical research, drug development and the delivery of patient treatments.
Source: MarketWatch Copyright © 2012 MarketWatch, Inc (21/05/12)
Stemcell therapy for multiple sclerosis is now a reality, not just a dream, says a leading neuro-immunologist.
Gianvito Martino, director of neuroscience at San Raffaele Hospital in Milan, Italy, said although the therapy was still experimental, it was yielding some exciting results.
Professor Martino said he did not believe stemcell therapy would be the solution to MS but an important treatment option with fewer side effects.
"To have the solution, we should know the cause of the disease but we don't know it," he said.
About 85 per cent of patients had relapsing remitting MS, which could be managed with current treatments, he said. However, within 10-20 years, about 90 per cent of these patients moved into the secondary progressive phase, for which there were no effective treatments, while about 10 per cent continued to have the so-called benign first phase.
"About 80-85 per cent of patients will need aid for walking in 20-25 years from diagnosis," he said.
The average age of diagnosis is 20-40. In Australia, three times as many females are affected. In the autoimmune disease, the insulating sheath of the nerve cells, called myelin, is attacked and destroyed and eventually the nerves are also destroyed, leading to progressive atrophy of the brain and spinal cord, which is the cause of disability. In Australia, the incidence of MS is about one in every 1000 people, with more than 21,000 people affected.
Professor Martino said there were two types of stemcells already being used in patients, both from blood. They were haematopoietic and mesenchymal stemcells.
Haematopoietic stemcells were those used in bone-marrow transplantations. The patient's immune system was destroyed by chemotherapy and then their own stemcells from the bone marrow were transplanted.
"The idea is to have new blood with no more cells capable of damaging your myelin," Professor Martino said.
"It is immuno- suppressive therapy, blocking the cells causing the disease."
About 500 MS patients worldwide had received the therapy since 1997 and in many, the progression of their disease had been halted.
"The results are very, very important because about 60 per cent of those patients do not worsen for up to four to five years after the transplants, they stabilise," Professor Martino said.
Even more exciting was the fact that only the patients with the worst prognosis and unresponsive to approved therapies had been eligible for the treatment, which was proving so successful.
Among those patients, the ones better responding to the transplant were the 5 per cent with the so-called malignant form of MS, who needed a wheelchair within five years of diagnosis.
The second type of transplant used mesenchymal cells, which are multi-potent stemcells taken from the blood and which can differentiate into a variety of cell types.
"They seem to help the immune system to block the body's reaction against itself," Professor Martino said. "You can just inject them intravenously and you don't need immuno-suppression or any therapy to avoid rejection."
While they seemed to block further damage from the disease, they did not repair nerve cells already damaged.
Apart from blood stemcells, there is another form of stemcell therapy which his group is testing, using neural stemcells taken from a foetus and grown in vitro as precursors of brain cells, which are then transplanted via a lumbar puncture.
"Those cells were not only able to become cells producing myelin once transplanted but they could also help cells resident within the brain, which were not damaged by the disease, to repair the brain," he said.
The trials conducted by his group to date have been in mice and monkeys. "We hope to start treatment in patients . . . within the next five years," he said.
He warned MS patients against going to the so-called stemcell clinics that were scattered worldwide, saying the therapy should be conducted only under rigorous clinical trial conditions.
Source: 'The West Australian' (c) West Australian Newspapers Limited 2012 (05/04/12)