For release: Tuesday, February 26, 2002
The brain produces new cells to repair the damage from multiple sclerosis (MS) for years after symptoms of the disorder appear, according to a recent study. However, in most cases the cells are unable to complete the repairs. These findings suggest that an unknown factor limits the repair process and may lead to new ways of treating this disorder.
"The brain is making a serious attempt to repair the damage," says Bruce D. Trapp, Ph.D., of the Cleveland Clinic Foundation in Ohio, who led the study. The findings are consistent with those of other recent studies showing that the adult brain has the capacity to replace cells, he adds. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and appears in the January 17, 2002, issue of The New England Journal of Medicine.
In patients with multiple sclerosis, brain inflammation in random patches, or lesions, leads to destruction of myelin, the fatty covering that insulates nerve cell fibers called axons in the brain and spinal cord and aids in transmission of signals to other neurons. This inflammation causes the myelin to deteriorate and leads to the symptoms of MS. Previous studies have shown that some brain lesions are repaired during the early years of multiple sclerosis. However, many other lesions are not repaired.
In the study, Dr. Trapp and colleagues examined brain tissue obtained during autopsies of 10 patients with MS to see if new myelin-producing cells, called oligodendrocytes, were being produced in the chronic MS lesions. They found that most of the lesions contained newly produced oligodendrocytes. The percentage of lesions from each brain that had these new cells decreased as the duration of the disease increased, but the decline was not related to the type of MS the patients had or to their ages at death. The new oligodendrocytes extended "arms" that produced myelin-related proteins and grew around the damaged axons as if they were trying to repair the myelin. However, in most cases the axons were not repaired.
One of the central questions in MS research is how to promote myelin repair. Many researchers have concentrated on increasing the number of oligodendrocytes through stem cell transplantation or other means. However, this study suggests that problems with the axons or with the tissue that surrounds them may prevent remyelination. Many of the axons that were not remyelinated looked abnormal, whereas remyelinated axons appeared healthy. This suggests that therapies which prevent axon degeneration or help oligodendrocytes complete the repair process in other ways may be necessary. More research is needed to identify drugs that may be useful for this purpose, says Dr. Trapp. While the study shows that the brain's attempts to repair itself decrease over time, new cells were produced even in patients who had had MS for as long as 15 years, implying that there is a long window of opportunity for treatment.
Researchers must now determine how long the new oligodendrocytes survive in the brain and whether the brain can produce enough of them to repair all the damage from MS, says Dr. Trapp. If the brain produces enough new cells on its own, then transplantation of additional cells may not be necessary. Research using brain scanning or other techniques may help to identify patients who are most likely to benefit from these therapies.
Reference: Chang A, Tourtellotte WW, Rudick R, Trapp BD. "Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis." The New England Journal of Medicine, Vol. 346, No. 3, January 17, 2002, pp. 165 - 173.
- By Natalie Frazin
Last Modified August 14, 2012