Decades of research into nerve physiology, MS tissue damage and the biology of glial cells – the numerous brain cells that support nerve cells – have been laying the groundwork for finding ways to restore normal function in individuals with MS.
Nervous System Repair and Protection teams funded by the Society’s Promise: 2010 initiative are taking this research to the next level, with a goal of placing nerve tissue-protective treatments in clinical trials by the year 2010.
Other research on this topic focuses on the micro-environment of the brain and conditions conducive to stimulating natural repair, and the potential for cell therapies. Exploring glia, which include cells in the nervous system that make nerve-insulating myelin, is a cornerstone of MS research. Myelin appears to be the main target of the immune attack in MS. The cells that make myelin—oligodendrocytes—also are lost in MS. Researchers study aspects of myelin that make it an immune target, and ways that some brain cells can contribute to the immune attack. They are also looking at factors that are important to the growth and development of oligodendrocytes and myelin, to find ways of promoting myelin repair.
Read more about myelin as an immune target and nervous system repair efforts in our brochure, “Research Directions.”
The aim of repairing the nervous system is to achieve an actual reversal of the damage caused by MS and to restore function. When myelin is damaged or destroyed, electrical conduction along the nerve fiber is impaired or stopped. Decades of research on myelin and myelin-making cells make it clear that natural myelin repair occurs, and key molecules and growth factors are being identified that may serve as targets for stimulating myelin repair. Read about recent Society-funded projects (from Fall 2009 [PDF] and Winter 2009 [PDF]) focusing on myelin.
In recognition that during the course of MS the nerve fibers, or axons, are also damaged, a new research focus has emerged: in order to repair the nervous system, we must learn how to regenerate axons as well as myelin. Insights into complex mechanisms involved in nervous system development now make it feasible to aggressively address the task of repairing axons as well as myelin in MS. Read about recent Society-funded projects (from Fall 2009 [PDF] and Winter 2009 [PDF]) focusing on nervous system repair.
Approaches to repairing the nervous system are varied. Some are aimed at inducing the body’s own cells to more adequately carry out the repair function. Another approach is to introduce replacement cells from a different source. Research into the potential of stem cell therapy is proceeding rapidly, using cells obtained from a variety of adult and non-adult sources. It is currently not clear which source of stem cells, if any, will be of value in treating people with MS. Similarly, if more than one source proves to be valuable, it is not clear which will be best.
The National MS Society and the MS International Federation sponsored a Stem Cell Summit meeting in January 2007 to begin to determine how best to answer these questions. Read a summary of findings (.pdf). This is a field that is in its earliest stages of development, and the Society is funding research studies that will lead to significant advances in our knowledge on this front.
In conjunction with the efforts to repair axons are new efforts to protect them from degeneration in the first place. For example, it is not clear whether axonal degeneration in MS results from a direct attack on axons by the immune system or, alternatively, if the loss of myelin by itself is enough to cause axonal degeneration (i.e., whether myelin has a protective effect on axons that is lost in the MS disease process). The protection of axons from these and other insults are a new area of intense research efforts in MS.
Targeted Initiative: Nervous System Repair and Protection
The Nervous System Repair and Protection Initiative, funded through Promise: 2010 is bringing the dream of protecting and repairing brain tissue and restoring function within our grasp.
Collaborative MS Research Centers Focused on Nervous System Repair
These special centers combine the expertise of top MS researchers with scientists outside the field of MS who are using cutting-edge technologies to engage in large-scale explorations, gaining from each other’s experience.
- Team leader Joel Levine, PhD (SUNY, Stony Brook) and colleagues are characterizing resident cells in the brain capable of repairing myelin and developing techniques and molecules to induce them to rebuild damaged tissues in MS and restore function.
- James Salzer, MD, PhD (New York University) and colleagues are investigating mechanisms that are critical for the initial events of immune-mediated myelin damage in MS and clarifying the sources of cells that might repair such damage to rebuild the nervous system.
- Jeffery D. Kocsis, PhD (Yale University) leads a team testing ways, such as cell transplantation, to protect and repair central nervous system tissue.
Other National MS Society-supported projects focusing on MS repair:
- Gareth John, VetMB, PhD (Mount Sinai School of Medicine) is studying a new role for brain cells called astrocytes, which may contribute to myelin repair in MS. Recent evidence suggests that factors produced locally within myelin-damaged areas (called lesions or plaques) play an important role in determining the success or failure of myelin repair. Dr. John’s team is studying astrocytes, which may contribute to myelin regeneration. Astrocytes release signaling chemical called IL-11, which may promote the survival and maturation of myelin making cells and increase their production of myelin. Dr. John’s team is tracing the signals and pathways activated by IL-11 that lead to myelin formation. They are also examining tissue samples of MS lesions to detect evidence of IL-11 activity in areas where myelin has been repaired. This research may open a therapeutic avenue to promote myelin repair in people with MS.
- Stefano Pluchino, MD, PhD (Fondazione Centro San Raffaele del Monte Tabor, Milan) is exploring mechanisms at work in the phenomena in which cell transplants can reduce brain inflammation and enhance nervous system tissue repair. This team and others have been investigating transplantation of neural stem cells. These cells have been shown to move to distant sites of injury within the brain upon intravenous injection, and may either develop into various functional types of brain cells—including neurons and myelin-forming cells—or eventually significantly suppress the burden of inflammation in specific areas of the brain. Now they are tracking these transplanted cells more closely in mice with MS-like disease to determine how they accumulate, persist, and affect the immune response. These findings are critical to the rational design and development of clinical trials for cell transplantation in people with MS.
- Howard Weiner, MD (Brigham and Women's Hospital) is conducting preclinical testing of a novel compound that has potential to protect nervous system tissues from MS inflammation. His team is continuing studies of a new drug called ABS-75 that has shown to be effective in treating progressive forms of EAE, the MS-like disease of mice. Some research suggests that overproduction of a nerve chemical called glutamate by immune cells may cause the nerve degeneration characteristic of progressive MS. Dr. Weiner is testing the effects of ABS-75 on glutamate synthesis and on the activation of immune cells called astrocytes, which have been implicated as key players in the MS immune response. ABS-75 is also being administered to mice with EAE to study potential side effects and dosing requirements, as well as to analyze how the drug works with the immune system to protect nerve cells.