Remyelination and multiple sclerosis: therapeutic approaches and challenges

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. After acute inflammatory mediated demyelination, some remyelination often occurs, but in chronic demyelinated MS plaques, remyelination frequently fails. Chronically demyelinated axons cause a variety of symptoms and probably are more likely to degenerate, leading to irreversible clinical disability. Oligodendrocyte precursor cells (OPCs) present in the adult brain can proliferate and differentiate to remyelinate lesions. Failure of remyelination in the majority of MS patients is secondary to arrest in OPC differentiation. Many therapies have been developed to modulate the immune response in MS, but no neuroprotective or remyelinating therapies are available. Promoting remyelination is a promising avenue for protecting axons, reversing neurologic disability and preventing progressive disease in MS. This review will begin with an overview of remyelination and remyelination failure, consequences of demyelination, and available animal disease models. In addition, preclinical and clinical studies on the most promising potential therapies for inducing remyelination will be described.