Targeting Oligodendrocyte Protection and Remyelination in Multiple Sclerosis

Authors

  • Jingya Zhang,

    1. Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY
    2. Department of Neurology, Mount Sinai School of Medicine, New York, NY
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  • Elisabeth G. Kramer,

    1. Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY
    2. Department of Neurology, Mount Sinai School of Medicine, New York, NY
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  • Sean Mahase,

    1. Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY
    2. Department of Neurology, Mount Sinai School of Medicine, New York, NY
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  • Dipankar J. Dutta,

    1. Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY
    2. Department of Neurology, Mount Sinai School of Medicine, New York, NY
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  • Virginie Bonnamain,

    1. Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY
    2. Department of Neurology, Mount Sinai School of Medicine, New York, NY
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  • Azeb T. Argaw,

    1. Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY
    2. Department of Neurology, Mount Sinai School of Medicine, New York, NY
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  • Gareth R. John

    Corresponding author
    1. Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY
    2. Department of Neurology, Mount Sinai School of Medicine, New York, NY
    • Mount Sinai School of Medicine New York, NY
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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. Mt Sinai J Med 78:244–257, 2011. © 2011 Mount Sinai School of Medicine

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