There are many types of stem cells that are undergoing research and which are producing knowledge about their potential use in treating MS. Many of these studies involve adult mesenchymal (pronounced messENkimmul) stem cells, which are present in many tissues of the body, including bone marrow and fat (adipose tissue). These cells are being tested for their ability both to treat immune disorders and promote tissue repair. Further study is necessary to determine what kind of cells might prove optimal for treating some or all people with MS.
Stem cell therapy, even in the controlled setting of a clinical trial, carries the possibility for substantial risks. Anyone who is considering enrolling in a clinical trial should evaluate carefully the potential adverse events that will be outlined in the “informed consent form” that trial participants must sign.
HSCT to Reboot the Immune System
Q. What is HSCT for multiple sclerosis?
A. HSCT (Hematopoietic Stem Cell Transplantation) attempts to “reboot” the immune system, which is responsible for damaging the brain and spinal cord in MS. In HSCT for MS, hematopoietic (blood cell-producing) stem cells, which are derived from a person’s own (“autologous”) bone marrow or blood, are collected and stored, and the rest of the individual’s immune cells are depleted by chemotherapy. Then the stored hematopoietic stem cells are reintroduced to the body. The new stem cells migrate to the bone marrow and over time produce new white blood cells. Eventually they repopulate the body with immune cells.
Q. What is the idea behind autologous HSCT for MS?
A. The goal of HSCT is to reset the immune system and stop the inflammation that contributes to active relapsing MS.
Q. Is HSCT an FDA-approved therapy option for people with MS?
A. No, HSCT is considered experimental for the treatment of multiple sclerosis.
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Recent HSCT Results
• A multi-center, 5-year trial called the HALT MS Study tested HSCT in 25 people with MS and active disease that was not controlled by disease-modifying medications. The trial was funded by the National Institutes of Health and the Immune Tolerance Network. Results presented at the June 2016 Annual Meeting of the Consortium of MS Centers suggest that after five years, 69% of participants experienced no new disease activity after the procedure and did not need disease-modifying therapies to control their disease. Most side effects related to blood cell reductions and infections. When the complete data are published, this trial 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.
• In June 2016 researchers in Canada published results of a long-term HSCT trial involving 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 experienced clinical relapses or required MS disease-modifying therapies to control their disease, and 40% experienced reductions in disability. One participant died and another required intensive hospital care for liver complications. All participants developed fevers, which were frequently associated with infections, and other toxicities. Read more about this study
• In October 2015, researchers at the University of Genoa and other institutions in Italy reported on a small trial of HSCT in seven people with very active relapsing-remitting MS that was not controlled with MS disease-modifying therapy. They underwent a “low-intensity lympho-ablative regimen” in which the immune system was suppressed but not completely depleted before the stem cell transplant as an approach to reducing toxicity. The investigators did MRI scans (for 3 years) and clinical evaluations (for 5 years). They found dramatic reductions of MRI-detected inflammation after the procedure, but did not achieve complete absence of inflammation. After 5 years, two participants remained stable, one significantly improved, and four had mild disease progression. One experienced a relapse after treatment. No severe side effects occurred. The authors conclude that the low-intensity regimen they used was not sufficient to treat aggressive MS. Read an abstract from the paper (Multiple Sclerosis 2015 Oct;21(11):1423-30)
• In January 2015, doctors at Northwestern University published their10-year experience of treating people with HSCT. The report included 123 people with relapsing-remitting MS and 28 with secondary-progressive MS. Their method is “nonmyeloblative” HSCT, in which the immune system is suppressed but not completely depleted before the stem cell transplant. Individuals were followed from 6 months to 5 years, or an average of 2.5 years. The EDSS disability scores improved, compared to pretreatment, by one point or more in 64% of those followed out to year 4. Relapses and MRI-detected disease activity were also reduced. In evaluating which type of individuals benefited from the therapy, the doctors suggested that people with relapsing-remitting MS who had had MS for ten years or less showed improvements in their disability scores, whereas those with secondary-progressive MS or disease duration greater than ten years did not show improvements on their disability scores. They reported no treatment-related deaths or serious infections. ITP (immune-mediated thrombocytopenia), a potentially serious bleeding disorder, developed in 7 people, and thyroid disorders developed in 7 people. Read a summary of their results or the paper in JAMA (Published online January 20, 2015).
Additional research is focusing on figuring out who might benefit from this procedure and how to reduce its risks. HSCT is being investigated in Canada, the United States, Europe and elsewhere. For example:
• An international clinical trial of this procedure, being led by Dr. Richard Burt of Northwestern University in Chicago, is now recruiting individuals who have not responded to other disease-modifying therapies. THIS TRIAL IS CURRENTLY RECRUITING PARTICIPANTS at its sites at Northwestern University, Rush University Medical Center, University of Sao Paulo, Uppsala University and Sheffield Teaching Hospitals NHS Foundation Trust. Read more about who may be eligible to participate. Dr. Burt and colleagues recently published a case series exploring outcomes for individuals who underwent the procedure.
Blogs About HSCT
Video: One woman’s journey with HSCT
Adult Mesenchymal Stem Cells to Reduce Disease and Augment Repair
Another experimental approach being tested in clinical trials is similar to HSCT, except that the individual’s immune cells are not destroyed or replaced. An individual’s own mesenchymal stem cells are isolated from the bone marrow or blood stream and multiplied in the lab, and then re-introduced in greater numbers into their body. This approach is being tested in several clinical trials including:
• A small, open-label, phase I clinical trial at Cleveland Clinic tested the ability of an individual’s own mesenchymal stem cells to both inhibit immune mechanisms and to augment intrinsic tissue repair processes in people with relapsing forms of MS. They were given intravenously (infused into the vein). This study was led by Dr. Jeffrey A. Cohen and supported by the Congressionally Directed Medical Research Programs. The National MS Society provided support for a pilot study related to this trial to compare stem cells from people with MS and controls without MS, looking at how the cells survive and function, to enhance understanding from this stem cell trial. This trial, which was designed to evaluate safety and not designed to determine benefits, was completed and preliminary results were presented in September 2014, suggesting that this approach was safe and warrants a phase 2 trial, which is now in planning stages. THIS PLANNED TRIAL IS NOT YET RECRUITING ADDITIONAL PARTICIPANTS.
• A small, open label, phase I stem cell trial has begun at the Tisch MS Research Center of New York using individuals’own mesenchymal stem cells to derive more specific stem cells called “neural progenitor cells.” The cells are expanded in the laboratory and then injected into the space around the spinal cord (intrathecal). The goal is to inhibit immune mechanisms and to augment tissue repair. THIS TRIAL IS ONGOING AND NOT SEEKING ADDITIONAL PARTICIPANTS.
Recently the Tisch Center team announced intentions of following-up on this work by conducting a phase II trial of this therapy. The National MS Society is currently in discussions with the team to determine how the proposed phase II trial may be funded in an expedited fashion, pending successful completion of the phase I trial, and that its results continue to show that the procedure is safe.
• An international, placebo-controlled, phase II stem cell trial involving people with MS who show specific signs of inflammation and active disease, including people with primary progressive MS, secondary-progressive MS and relapsing-remitting MS, is getting underway at multiple sites in Europe and Canada. The “MESEMS” trial will test benefits and safety of using individuals’ own bone marrow cells, which are extracted and then given by intravenous infusion immediately or six months after extraction. The goal is to inhibit immune mechanisms and to augment tissue repair. THIS TRIAL IS BEGINNING TO RECRUIT PARTICIPANTS. GO TO THE MESEMS WEBSITE FOR FURTHER INFORMATION ABOUT LOCATION AND CONTACT INFORMATION.
• A small, open label, phase I trial of stem cells derived from placenta (known as “PDA-001” manufactured by Celgene Cellular Therapeutics) was completed in 2014, and results suggested this approach was safe. The study involved 16 people with relapsing-remitting or secondary-progressive MS at sites in the U.S. and Canada. This study was designed to evaluate safety and not designed to show effectiveness. In the published paper, the researchers comment that the next step, a proof-of-concept clinical trial, is planned. THIS PLANNED NEXT TRIAL IS NOT YET RECRUITING PARTICIPANTS.
• A placebo-controlled, phase II stem cell trial involving people with secondary-progressive MS and primary progressive MS has begun at Frenchay Hospital in Bristol, United Kingdom, testing the benefits and safety of using individuals’ own bone marrow cells. The cells are extracted and then given by intravenous infusion immediately or one year after the extraction. The goal is to inhibit immune mechanisms and to augment tissue repair. THIS TRIAL IS RECRUITING PARTICIPANTS AT ONE SITE IN THE UNITED KINGDOM.
Larger, longer-term, controlled studies are needed to determine the safety and effectiveness of using stem cells to treat MS. When the results of these and subsequent clinical trials are available, it should be possible to determine what the optimal cells, delivery methods, safety and actual effectiveness of these current experimental therapies might be for different people with MS. Read more about stem cell clinics.
Other Stem Cell Research
Another line of stem cell research in MS relates to efforts to repair nervous system damage directly with stem cells that may replace the cells that make myelin, the protective cover on nerve wires which is damaged during MS, and nerve cells that have been destroyed. One exciting avenue being explored in early stages is the concept of taking samples of a person’s skin cells and turning them into stem cells. These cells are called “induced pluripotent stem cells” or iPSC. The potential advantage of this approach is that it’s possible such cells would not be rejected by the person’s immune system, and this approach bypasses possible ethical concerns connected with human embryonic stem cells.
This research is still in its infancy as studies proceed to determine whether any types of stem cells can reverse MS damage and restore function. Read more about efforts to repair the nervous system.
Read about National MS Society Research in Stem Cells
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