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Stem cells hold promise for MS

Stem cells

There is exciting and innovative research and progress occurring related to the potential of many types of stem cells for slowing MS disease activity and for repairing damage to the nervous system. In light of the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, we believe that the potential of all types of cell therapies must be explored.

Stem cell therapy is any treatment that uses or targets stem cells, which are the types of cells that differentiate into many different specialized cells in our bodies. Stem cells are found in both embryos and adults.

Many types of stem cells are being explored for their potential benefits for treating multiple sclerosis. Only when the results of these and subsequent clinical trials are available will it be possible to determine what the optimal cells, delivery methods, safety and actual effectiveness of these current experimental therapies might be for people with MS.

Although cell based therapy has generated a great deal of interest and holds promise, the field is in its infancy and much more research is needed before cell based therapies become a MS treatment option.

Different Types of Stem Cells

  • HSCs (haematopoietic stem cells) – adult stem cells that are found in bone marrow and blood. HSCs are capable of producing all of the cells that make up the blood and the immune system.
  • MSCs (mesenchymal stem cells) – adult stem cells found in several places in the body, including the bone marrow, skin and fat tissue. They produce cells which help other stem cells function properly.
  • NSCs (neural stem cells) – specialized stem cells responsible for repairing nerve-insulating myelin in the brain. These can be derived from other types of stem cells such as mesenchymal cells.
  • hESCs (human embryonic stem cells) – stem cells derived from donated embryos. They can naturally produce every type of cell in the body. One concern about their potential therapeutic use is that they have been found to cause tumors.
  • iPSCs (induced pluripotent stem cells) are engineered from adult cells to produce many types of cells. One concern about their potential therapeutic use is that they have been found to cause tumors.

www.nmss.org  The National Multiple Sclerosis Society

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Study Shows Expansion of Stem Cell Clinics in the U.S. and the Need for Better Oversight

Researchers have published a paper describing the proliferation of stem cell clinics in the United States and ethical issues and regulatory concerns that come with marketing unproven treatments for many conditions. Their study shows that many different types of unproven stem cell treatments are being offered, and highlights concerns for the safety of people who undergo these treatments.

There is exciting progress being made through innovative research related to the potential of many types of stem cells for slowing MS disease activity and for repairing damage to the nervous system. At present, there are no approved stem cell therapies for MS. People need the best available information to understand this exciting area of research and make decisions related to this complex issue.

The paper’s findings support the need for stem cell therapy to be explored in the context of carefully conducted clinical trials that can determine what the optimal cells, delivery methods, safety and actual effectiveness of cell therapies might be for people with MS.

Positive Results from Study of Bone Marrow-Derived Stem Cells in People with Aggressive, Relapsing MS

Summary

  • Researchers in Canada have published results of a long-term trial of an individuals’ own (autologous) hematopoietic (blood cell-producing) stem cell transplantation. The study involved 24 people with aggressive relapsing-remitting MS whose disease was not controlled with available therapies.
  • Three years after the procedure, 70% remained free of disease activity, with no relapses, no new MRI-detected inflammatory brain lesions, and no signs of progression.
  • None of the surviving participants, who were followed for 4 to 13 years after the procedure, experienced clinical relapses or required MS disease-modifying therapies to control their disease, and 40% experienced reductions in disability.
  • One of the participants died and another required intensive hospital care for liver complications. All participants developed fevers, which were frequently associated with infections, and other toxicities.
  • Additional research is focusing on figuring out who might benefit from this procedure and how to reduce its risks.

“These results suggest that aggressive MS may be stopped with an effective but risky procedure, for a subset of people,” said Dr. Bruce Bebo, Executive Vice President, Research, at the National MS Society. “Additional research by investigators around the world is focusing on figuring out who might benefit from this procedure and how to reduce its risks, which can include death.”

Details
Background: An experimental procedure that has been explored for several years in MS is called “autologous hematopoietic (blood cell-producing) stem cell transplantation” – or HSCT. This procedure has been used in attempts to “reboot” the immune system, which launches attacks on the brain and spinal cord in people with MS.

In HSCT, the stem cells (derived from a person’s own bone marrow or blood) are stored, and the rest of the individual’s immune cells are depleted by chemotherapy. Then the stored stem cells are reintroduced by infusion into the vein. The new stem cells migrate to the bone marrow and over time produce new blood cells, including immune cells. The goal of this currently experimental procedure is to establish a new immune system that no longer recognizes myelin and other nervous system tissue as dangerous. In theory, this should stop the attacks that lead to tissue damage and disability.

There are a number of laboratories around the world testing variations of HSCT for the treatment of autoimmune diseases, including MS. Preliminary findings suggest this is a promising, but potentially risky strategy for the treatment of MS.

The Study: Drs. Harold Atkins, Mark Freedman and team at the Ottawa Hospital, University of Ottawa and other institutions in Canada conducted a Phase 2 trial of HSCT that involved 24 people with aggressive relapsing-remitting MS whose disease was not controlled with available therapies. No control group was used which would have enabled comparison against the results found in the treatment group. The procedure used by this group included complete destruction of bone marrow cells and an additional step that enriched the transplanted cells for stem cells.

Results – Safety: One of the participants died of transplantation-related complications that caused liver failure and another required intensive hospital care for liver complications. The treatment regimen was modified over the course of the study to reduce toxicity, but all participants still developed fevers, which were frequently associated with infections.

Results – Effectiveness: Three years after the procedure, 70% of the participants remained free of disease activity, meaning they had no relapses, no new MRI-detected inflammatory brain lesions, and no signs of progression. The remaining 30% experienced progression of disability. In addition, for the entire follow-up period ranging from 4 to 13 years after the procedure, of the 23 survivors:

  • None experienced clinical relapse, had new active inflammatory MRI brain lesions, or required MS disease-modifying therapies to control their disease.
  • The average rate of brain atrophy (shrinkage), a measure that has been linked to MS progression, returned to levels associated with normal aging.
  • 40 percent experienced some lasting reversal of disability such as vision loss, muscle weakness and balance problems.
  • Some were able to return to work or school.

The results were published online on June 9, 2016 in The Lancet.  Major funding for the study came from the MS Society of Canada and its affiliated Multiple Sclerosis Scientific Research Foundation.

Next Steps: Rigorous clinical trials of stem cell therapies are needed to determine their safety and effectiveness in people with MS. Trials of this and other stem cell therapy approaches are taking place in Canada, the United States, Europe and elsewhere. To help explore the potential of stem cell therapy, in November 2015, the International Conference on Cell-Based Therapy for Multiple Sclerosis was convened in Lisbon, Portugal under the auspices of the International Advisory Committee on Clinical Trials in MS (a group jointly sponsored by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis). Seventy leading researchers and clinicians conferred on clinical trials needed to provide answers about which types of cells, which route of delivery, and which types and stages of disease, would be the most promising approach for treating MS. Read more about this meeting

Read more about stem cells and MS

The Latest on Stem Cell Treatment

Recent media reports have featured news about a clinical trial involving harvesting a person’s own stem cells to treat aggressive multiple sclerosis.
• This treatment, called autologous haematopoietic stem cell transplant (HSCT), attempts to “reboot” the immune system, which is believed to launch attacks on the brain and spinal cord in people with MS.
• HSCT is under investigation in clinical trials in Canada, the United States, Europe and elsewhere. Clinical trials are needed to fully understand the benefits and risks of HSCT in MS, and who might benefit most from this approach, since it does not seem to be effective in all types of MS.
• In HSCT, stem cells from a person’s own bone marrow or blood are stored, and the rest of the individual’s immune cells are depleted usually by chemotherapy. Then the stored stem cells are reintroduced and over time they produce new cells that repopulate the body with immune cells.
• There is exciting progress being made through innovative research related to the potential of many types of stem cells both for slowing MS disease activity and for repairing damage to the nervous system.
• At present, there are no approved stem cell therapies for MS. Stem cell therapy is in the experimental stage, and it’s important for people to have the best available information to understand this exciting area of research and make decisions related to this complex issue.
• In November 2015, the International Conference on Cell-Based Therapy for Multiple Sclerosis was convened by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis, bringing leading researchers and clinicians together to confer on clinical trials needed to provide answers about which types of cells, which route of delivery, and which types and stages of disease, would be the most promising approach for treating MS. A summary and consensus on next steps will be published by the conference organizers, with recommendations to help speed the development of new cell-based treatment solutions.
• With the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, we believe that the potential of all types of cell therapies must be explored. The Society is currently supporting 12 research projects exploring various types of stem cells, including cells derived from bone marrow, fat and skin, and has supported 68 stem cell studies over the past 10 years.

Interim Results Reported from Clinical Trial of Stem Cell Transplantation in People with Relapsing-Remitting MS

A nationwide team of researchers report on interim results from a small, five-year study of transplantation of the individuals’ own hematopoietic (blood cell-producing) stem cells combined with high-dose immunotherapy in 24 people with relapsing-remitting MS. This procedure aims at “rebooting” the immune system to prevent MS immune attacks against the brain and spinal cord. At three years, 78.4% of participants experienced no new disease activity. When this trial has completed its five-year duration, it will be an important addition to research needed to determine whether this approach to stem cell transplantation is safe and effective in people with MS. Richard A. Nash, MD (Colorado Blood Center Institute) and colleagues report in JAMA Neurology (Published online December 29, 2014). This study was sponsored by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Background: One type of procedure that has been explored for many years in MS is called “autologous hematopoietic (blood cell-producing) stem cell transplantation” – or HSCT. This procedure has been used in attempts to “reboot” the immune system, which launches attacks on the brain and spinal cord in people with MS.
In HSCT, these stem cells (derived from a person’s own bone marrow or blood) are stored, and the rest of the individual’s immune cells are depleted usually by chemotherapy. Then the stored stem cells are reintroduced back to the individual’s bloodstream. The new stem cells migrate to the bone marrow and over time produce new cells. Eventually they repopulate the body with immune cells. The goal of this currently experimental procedure is that the new immune cells will no longer attack myelin or other brain tissue, providing the person, what is hoped to be, a completely new immune system.
The Study: Investigators enrolled 25 people who had experienced an MS relapse involving loss of neurologic function while taking disease-modifying therapies during the previous 18 months. Participants received HSCT along with high-dose immunosuppressive therapy (a regimen of treatments that profoundly suppress the immune system), and followed for five years. The primary endpoint of this study is whether participants experience “event-free survival,” meaning that they did not die or have an increase in disease activity. Disease activity is defined as any one of the following outcomes occurring: confirmed loss of neurologic function, clinical relapse, or new lesions observed on MRI scans. The current publication presents a planned analysis after three years of follow up.
Results: One individual experienced a pulmonary embolism induced by heparin (administered as part of stem cell collection), and withdrew from the study. Event-free survival at three years was 78.4%, down from 95.8% after one year. Treatment failed in five individuals. Scores on clinical scales measuring disease activity and quality of life, including the EDSS, improved significantly at three years after HSCT. Immune system analysis showed prolonged depletion of the immune cells that drive the immune attack, indicating that the immune system was indeed “rebooted.”
Two deaths occurred, one from complications due to MS progression and another due to asthma. One person experienced an MS attack, an individual who had not complied with a prednisone regimen designed to reduce this risk during collection of stem cells. There were 130 adverse events that were severe or life-threatening, mostly cytopenias (blood cell reductions) and infections.
Comment: Rigorous clinical trials of stem cell therapies are crucial to determining their safety and effectiveness in people with MS. “We look forward to seeing the completed results of this important study,” says Bruce Bebo, PhD, Executive Vice President of Research at the National MS Society. “There are significant risks involved in hematopoietic stem cell transplantation, and it’s important to ensure that this will be a safe solution for people with MS, with significant clinical benefit.”
With the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, the National MS Society believes that the potential of all types of cell therapies must be explored. The Society is currently supporting 15 research projects exploring various types of stem cells, including cells derived from bone marrow, fat and skin, and has supported 70 stem cell studies over the past 10 years.

Teams Report Success Enhancing Myelin Repair in Mice Using Stem Cells and Other Novel Approaches

Two teams of researchers funded in part by the National MS Society report success in stimulating the repair of nerve-insulating myelin in mouse models of MS. Myelin is a major target of immune attacks in MS, and although these are early results and further work is needed, these findings show some promise for strategies to repair damage and restore function for people with multiple sclerosis.

Background: In MS, myelin, the material that surrounds and protects nerve fibers, is damaged in the brain and spinal cord, and so are the cells that make myelin, called oligodendrocytes. Though the replacement cells that could repair myelin, called oligodendrocyte precursor cells (OPCs), exist in the brain, in MS they cannot adequately repair the damaged myelin.

Stem Cell Study: Lu Chen, PhD, Thomas Lane, PhD (University of California, Irvine) and colleagues report that administering neural precursor cells (nerve stem cells) to mice with MS-like disease reduced inflammation, decreased myelin damage, and increased myelin repair.

The team injected the stem cells into the spinal cord of mice with an MS-like disease induced by a virus. Although the stem cells were rejected by the body, and were not detectable within eight days after transplant, they were effective nevertheless in reducing the disease. Improvements in motor abilities of the treated mice were still apparent after six months.

The team noted that improvements went along with an increase in a type of immune cell called “regulatory T cells,” or “Tregs.” To test whether the Tregs contributed to the improvements, they blocked Tregs activity, which reduced the stem cells treatments’ impact.

The team speculates that the stem cells may be stimulating the immune environment in a way that activates mouse OPCs, even though the stem cells themselves do not turn into myelin-making OPCs. They are now investigating this idea further to discover the factors released by the stem cells. Ultimately, this information could contribute to the development of stem cell therapies and even cell-free therapies that stimulate recovery in people with MS.

Stimulating Resident Cells: Jessica Williams, PhD, Robyn S. Klein, MD, PhD, and colleagues (Washington University School of Medicine) report that targeting a signaling receptor (docking site) called “CXCR7” on immature oligodendrocytes in mice enhances myelin repair.

Dr. Klein’s team focused on a messenger protein (chemokine) that interacts with the immature OPCs. They studied mice that were given a toxin called cuprizone, which mimics myelin damage that occurs in the brain during MS. Once cuprizone is withdrawn, myelin repair occurs. The team found that CXCR7 activity increased during myelin damage, and then reduced with myelin repair. When the team administered an experimental compound that inhibits CXCR7, the numbers of OPCs, as well as mature oligodendrocytes, increased within myelin-damaged areas. Myelin repair was enhanced.

These data suggest that CXCR7 might serve as an important therapeutic target to promote myelin repair. Since these studies were conducted in mice, further research is necessary to ultimately determine whether this approach might be an effective approach for stimulating myelin repair in people with MS.

Conclusion:  Achieving success in the Society’s priority area of nervous system repair would provide life-changing advances for people with MS.

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