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Olesoxime accelerates myelination and promotes repair in models of demyelination

Authors

  • Karine Magalon MSc,

    1. Developmental Biology Institute of Marseille-Luminy, French National Center for Scientific Research Joint Research Unit n° 6216, Universite de la Mediterranee
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  • Celine Zimmer PhD,

    1. Developmental Biology Institute of Marseille-Luminy, French National Center for Scientific Research Joint Research Unit n° 6216, Universite de la Mediterranee
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  • Myriam Cayre PhD,

    1. Developmental Biology Institute of Marseille-Luminy, French National Center for Scientific Research Joint Research Unit n° 6216, Universite de la Mediterranee
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  • Joseph Khaldi MSc,

    1. Developmental Biology Institute of Marseille-Luminy, French National Center for Scientific Research Joint Research Unit n° 6216, Universite de la Mediterranee
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  • Clarisse Bourbon MSc,

    1. Biological and Medical Magnetic Resonance Center, French National Center for Scientific Research Joint Research Unit n° 6612, Faculty of Medicine, Universite de la Mediterranee
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  • Isabelle Robles MSc,

    1. Developmental Biology Institute of Marseille-Luminy, French National Center for Scientific Research Joint Research Unit n° 6216, Universite de la Mediterranee
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  • Gwenaëlle Tardif MSc,

    1. Trophos SA, Luminy Biotech Enterprises, Marseille, France
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  • Angèle Viola PhD,

    1. Biological and Medical Magnetic Resonance Center, French National Center for Scientific Research Joint Research Unit n° 6612, Faculty of Medicine, Universite de la Mediterranee
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  • Rebecca M. Pruss PhD,

    1. Trophos SA, Luminy Biotech Enterprises, Marseille, France
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  • Thierry Bordet PhD,

    1. Trophos SA, Luminy Biotech Enterprises, Marseille, France
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  • Pascale Durbec PhD

    Corresponding author
    1. Developmental Biology Institute of Marseille-Luminy, French National Center for Scientific Research Joint Research Unit n° 6216, Universite de la Mediterranee
    • IBDML, Parc Scientifique de Luminy, avenue de Luminy, case 907, 13288 Marseille cedex 9, France
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Abstract

Objective:

Multiple sclerosis is a neurodegenerative disease characterized by episodes of immune attack of oligodendrocytes leading to demyelination and progressive functional deficit. One therapeutic strategy to address disease progression could consist in stimulating the spontaneous regenerative process observed in some patients. Myelin regeneration requires endogenous oligodendrocyte progenitor migration and activation of the myelination program at the lesion site. In this study, we have tested the ability of olesoxime, a neuroprotective and neuroregenerative agent, to promote remyelination in the rodent central nervous system in vivo.

Methods:

The effect of olesoxime on oligodendrocyte progenitor cell (OPC) differentiation and myelin synthesis was tested directly in organotypic slice cultures and OPC–neuron cocultures. Using naive animals and different mouse models of demyelination, we morphologically and functionally assessed the effect of the compound on myelination in vivo.

Results:

Olesoxime accelerated oligodendrocyte maturation and enhanced myelination in vitro and in vivo in naive animals during development and also in the adult brain without affecting oligodendrocyte survival or proliferation. In mouse models of demyelination and remyelination, olesoxime favored the repair process, promoting myelin formation with consequent functional improvement.

Interpretation:

Our observations support the strategy of promoting oligodendrocyte maturation and myelin synthesis to enhance myelin repair and functional recovery. We also provide proof of concept that olesoxime could be useful for the treatment of demyelinating diseases. ANN NEUROL 2012;71:213–226

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