Targeting oligodendrocyte protection and remyelination in multiple sclerosis

Mt Sinai J Med. 2011 Mar-Apr;78(2):244-57. doi: 10.1002/msj.20244.

Abstract

Multiple sclerosis is an inflammatory demyelinating disease of the brain and spinal cord with a presumed autoimmune etiology. Conduction block in demyelinated axons underlies early neurological symptoms, whereas axonal transection is believed responsible for more permanent later deficits. Approved treatments for the disease are immunoregulatory and reduce the rate of lesion formation and clinical exacerbation, but are only partially effective in preventing the onset of disability in multiple sclerosis patients. Approaches that directly protect myelin-producing oligodendrocytes and enhance remyelination may improve long-term outcomes and reduce the rate of axonal transection. Studies in genetically modified animals have improved our understanding of mechanisms underlying central nervous system pathology in multiple sclerosis models, and have identified pathways that regulate oligodendrocyte viability and myelin repair. However, although clinical trials are ongoing, many have been unsuccessful, and no treatments are yet approved that target these areas in multiple sclerosis. In this review, we examine avenues for oligodendrocyte protection and endogenous myelin repair in animal models of demyelination and remyelination, and their relevance as therapeutics in human patients.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity / drug effects
  • Axons / drug effects
  • Axons / metabolism
  • Axons / pathology
  • Encephalomyelitis, Autoimmune, Experimental
  • Gene Regulatory Networks / immunology*
  • Humans
  • Immunologic Factors* / metabolism
  • Immunologic Factors* / therapeutic use
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Molecular Targeted Therapy
  • Multiple Sclerosis* / drug therapy
  • Multiple Sclerosis* / genetics
  • Multiple Sclerosis* / pathology
  • Multiple Sclerosis* / physiopathology
  • Myelin Sheath* / metabolism
  • Myelin Sheath* / pathology
  • Neuroprotective Agents / therapeutic use
  • Oligodendroglia* / drug effects
  • Oligodendroglia* / metabolism
  • Oligodendroglia* / pathology
  • Spinal Cord Regeneration / drug effects*
  • Spinal Cord Regeneration / immunology
  • Therapies, Investigational

Substances

  • Immunologic Factors
  • Neuroprotective Agents