More MS news articles for Jan 2002

Investigators Suggest That Factors In Long-Standing MS Brain Lesions May Inhibit Myelin Repair

January 18, 2002
Research Programs Department

Cleveland Clinic investigators examined long-standing MS brain lesions in tissue samples of 10 brains for evidence of repair of nerve-insulating myelin:


Investigators at the Cleveland Clinic Foundation published findings in the January 17, 2002 issue of The New England Journal of Medicine on the cells that make and replace myelin in and around long-standing, or chronic, MS brain lesions. Lesions are patches where myelin, the insulating coating on nerve fibers, has been destroyed and where nerve fibers may be damaged. The investigators, including Drs. Ansi Chang and Bruce Trapp, found evidence that the brain makes major attempts to repair itself, with myelin-making cells, called oligodendrocytes, present within lesion areas. However, the appearance and condition of the oligodendrocytes suggest that the cells are unable to complete the steps needed to move toward replacing myelin. These cells present a potential target for the development of therapies that can push them into the final steps of myelination to repair the damage caused by MS.


Multiple sclerosis develops when the immune system launches an attack against the myelin casing that surrounds and insulates nerve fibers in the brain and spinal cord. Other targets include the oligodendrocytes that are responsible for making and maintaining myelin and the nerve fibers (axons) that conduct signals in the nervous system. Although the body is capable of repairing some of the myelin that has been destroyed, most MS lesions are not repaired. One focus of MS research is to find ways to stimulate myelin repair, either by enhancing natural repair processes or by transplanting myelin-making cells into the brain in hopes they can survive and replace damaged myelin. Dr. Trapp’s team examined characteristics of oligodendrocytes that remained in MS lesions to determine whether there are any factors that limit their ability to repair myelin.


The team evaluated 48 “chronic” MS lesions (long-standing patches of myelin damage showing little immune activity, as opposed to active, acute lesions showing signs of immune attack) from autopsied brain specimens of 10 individuals, most of whom had progressive forms of multiple sclerosis in their lifetimes. They used several tissue staining techniques to discern immature oligodendrocytes from mature oligodendrocytes present in chronic lesions and, for comparison, in more active, acute lesions. They also examined “premyelinating” oligodendrocytes, which is their term for mature cells that extend “arms” reaching toward an axon as a first step before actually wrapping a myelin sheath around the axon.


The investigators found an abundance of premyelinating oligodendrocytes in 34 of 48 (71 percent) chronic lesions examined, regardless of individuals’ age and type of MS. The premyelinating oligodendrocytes extended processes toward axons, and showed signs of myelin protein production, but failed to begin to wrap myelin around them. Many chronic lesions showed signs of myelin repair at their borders. In these border areas showing signs of myelin repair, the axons appeared healthier than those within the lesions. The unhealthy axons within the lesions tended to be less straight and had areas of swelling.


Axons are thought to help guide the production of myelin by oligodendrocytes through the exchange of chemical signals and in other ways. The investigators speculate that the nerve fibers in chronic lesions do not support myelination and create conditions unfavorable to myelin replacement. This research presents potential targets for the development of new therapies that can push myelin-making cells into the final stages of myelin repair.

Additional research geared to understanding how oligodendrocytes and axons interact normally and in MS lesions should also help to scientists to develop effective myelin-repair strategies. These and many other research approaches to repairing the damage wrought by MS are currently underway.

© 2002 The National Multiple Sclerosis Society