Discovery opens new opportunities to slow or reverse MS

November 29, 2018
A new study shows an overlooked source may be able to replace lost nerve insulation and provide a new way to treat multiple sclerosis. The discovery of mature myelin-producing cells' capacity for repair opens new opportunities to slow or reverse the disease. That may call for new therapeutic approaches that rally the oligodendrocytes to reach out with new lifelines to damaged myelin sheaths.

Consensus has held that once an axon is robbed of its myelin, the only way to bring it back is by starting with fresh oligodendrocytes. Only oligodendrocytes arising from precursors called oligodendrocyte progenitor cells can apply a new coat of myelin to axons. Thus, MS treatments aimed at remyelination have focused on recruiting progenitor cells in demyelinated areas and spurring them to develop.

However, researchers at the University of Wisconsin-Madison's School of Veterinary Medicine have shown in a new study that starting from progenitor cells is not the only route to remyelination. In cats and rhesus macaques experiencing a severe loss of myelin, the study’s authors found fully developed oligodendrocytes already in place were reaching out and beginning to coat affected axons with myelin once again. The catch is that to be helpful and remyelinate damaged axons, the adult oligodendrocytes may still need to have connections to surviving myelin segments – called internodes – on other axons.

Cats fed irradiated food for several months developed severe myelin loss throughout the nervous system. When the cats returned to a regular diet, nerve function was restored because of extensive myelin repair. The cats' demyelination problems are unusual as a lab model of the disease.

In the new study, the researchers looked at the cats' nervous tissue and found a unique myelin mosaic – axons surrounded by thick layers of myelin (formed during development when the axons themselves grew) were interspersed with other axons surrounded by thin layers of myelin. The researchers found oligodendrocytes connected to both thick and thin myelin sheaths in the cat spinal cord.

They also found this association when they reached back to a decades-old monkey model of demyelination. The monkeys' myelin lesions resembled those in the cats.

Results of animal model studies sometimes do not translate to humans. According the researchers, the process may not be playing out in human MS patients fast enough to help mitigate the progression of the disease. Or too many oligodendrocytes may lose so many of their internodal connections that they become inactive or die.

The study was published in the Proceedings of the National Academy of Sciences.

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