Remyelination therapy for multiple sclerosis.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin and axons. All therapeutics used to treat MS have been developed to target an overactive immune response, with aims to reduce disease activity. Chronic demyelinated axons are further prone to irreversible damage and death, and it is imperative that new therapies address this critical issue. Remyelination, the generation of new myelin in the adult nervous system, is an endogenous repair mechanism that restores function of denuded axons and delays their deterioration. Although remyelination can be extensive in some patients, the majority of cases limit repair only to the acute phase of disease. A significant current drive in new MS therapeutics is to identify targets that can promote remyelination by boosting endogenous oligodendrocyte precursor cells to form new myelin. Also, a number of inhibitory pathways have been identified in chronic MS lesions that prevent oligodendrocyte precursor cells from being properly recruited to demyelinated lesions or interfere with their differentiation to myelin-forming oligodendrocytes. In this review, we introduce the phenomenon of remyelination from the view of experimental models and studies in MS patients, describe a potential role in remyelination for currently available MS mediations, and discuss many avenues that are being actively studied to promote remyelination. The next frontier in MS therapeutics will supplement immunomodulation with agents that directly foster myelin repair, with aims to delay disease progression and recover lost neurological functions.
Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
Michael B
MB
Keough
V Wee
VW
Yong
D000818:Animals; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology*; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology*
D007155:Immunologic Factors