What if we could actually reverse the damage that MS causes, restoring function to those who have been living with the disease for years? MS occurs when the immune system attacks the myelin coating that insulates nerve fibers in the brain and spinal cord; damage to nerve fibers — axons — also occurs, and underlies the progressive disability experienced by people with MS. The Nervous System Repair and Protection Initiative, funded through the Society’s Promise: 2010 Campaign, is bringing the dream of protecting and repairing brain tissue and restoring function within our grasp.
A specially convened National MS Society Task Force determined that the best way to speed up nerve tissue repair is to bring together experts in clinical trials and basic laboratory scientists to form partnerships. These teams could conduct all elements of the study from basic research to planning studies of neuroprotective drugs and repair strategies in people with MS.
Based on these recommendations, the Society awarded the largest grants ever made for research aimed at protecting and reversing neurological damage and restoring function in people with MS. Four teams in the U.S. and Europe are using nearly $15 million to lay the groundwork for clinical trials by 2010. This funding level allows scientists to attract more “heads and hands” to the problem, and to utilize the best available technology and develop needed new technologies to achieve our goals.
The four teams:
- Dr. Peter A. Calabresi (Johns Hopkins University) and collaborators are searching for better ways to detect and quantify tissue injury in MS and testing agents that may protect the nervous system from further damage.
- Professor Charles ffrench-Constant (University of Edinburgh, UK) and colleagues are focusing on restoring myelin by identifying and amplifying natural repair factors in the brain and by attempting to transplant replacement cells.
- Dr. Gavin Giovannoni (Queen Mary University of London, UK) and collaborators are attempting to turn cells into vehicles that will deliver repair molecules to sites of injury in the brain, and screening molecules for their protective properties as a prelude to clinical trials.
- Professor Ian D. Duncan (University of Wisconsin-Madison) is leading a multidisciplinary team to develop better imaging technologies such as PET and MRI to visualize myelin and nerve fiber damage, and to detect its repair. They are also exploring techniques for transplanting cells to promote repair.
Download a report (.pdf) evaluating the outcomes of this important initiative
Previously Reported Progress
- Dr. Calabresi’s team reported exciting results on myelin-associated glycoprotein (MAG), a protein in myelin; his team showed for the first time that MAG promotes resistance to nerve fiber injury and prevents nerve fiber degeneration both in cells isolated in the laboratory and in mouse models.
- Dr. ffrench-Constant’s team has identified a group of genes that are “turned on” following myelin damage, and may play a role in forming new myelin. These genes, called RXR, and RXR-gamma, are found in tissue damage isolated from people with MS. The team showed that a compound that promotes RXR activity promoted maturation of myelin-forming cells in the lab and in rodent models. On the flip side, this team conducted a genome-wide analysis that highlighted a specific genetic pathway (WNT) that may slow down myelin repair in MS. Now they are testing new therapeutic strategies in mice that lack components of the WNT pathway.
- Dr. Duncan reported that his team was able to generate immature myelin-making cells from human adult fibroblasts (stem cells involved in tissue structure and wound-healing).
- Dr. ffrench-Constant reported several findings about molecules that affect the maturation and migration of cell transplants: His group found that a combination of growth factors helps prolong the life of myelin-making cells taken from humans and isolated in the lab; these growth factors also promote the ensheathment of myelin around nerve fibers. They also showed that the protein activin hampers maturation of nerve cells, and they are currently defining these signals further. They also found that an immune system molecule, CD44, is essential for the trafficking of nerve cells and may regulate the transit of transplanted cells through the blood-brain barrier.
- Dr. Duncan’s team is working on improving the MRI detection of superparamagnetic iron-oxide particles that could be used to label and track cells used in transplant strategies. Dr. Calabresi’s team continues to conduct extensive studies of optical coherence tomography scanner, or OCT, a small, easy-to-use device that can be used in a doctor’s office. It measures the thickness of the nerve layer at the back of the eye (retinal nerve fiber layer), and can detect thinning of that layer in people with all types of multiple sclerosis. They have collected information on more than 1,000 people with MS to determine if this method can detect changes that occur over time – this kind of tracking of nerve fiber damage would be invaluable in MS management.
- Ancillary to the repair initiative, Dr. Giovannoni reported progress on a large multicenter study investigating whether the active compound in cannabis, THC (Tetrahydrocannabinol, which has shown benefit in pre-clinical studies), can slow MS progression. The study is fully enrolled and results are expected in late 2011.
- In addition, two of the teams are about to launch new, small-scale clinical trials, also with separate funding. One will investigate the safety of treatment with bone marrow stem cells; the other will attempt injections of neural stem cells. Both trials are fully enrolled and awaiting further funding and approvals. It is not clear yet whether either of these cell types will actually serve as replacement cells to restore brain tissue. Research in animal models suggests that these cells may create an environment that stimulates repair by resident cells. More research, which is ongoing, will help bring clarity to these and other questions.
Final Progress and Next Steps
These four multinational, interdisciplinary teams met recently in New York City to discuss accomplishments during the last five years, and to look toward the future. Read more about this meeting.