Olesoxime accelerates myelination and promotes repair in models of demyelination.

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.

• Authors: Karine Magalon, Celine Zimmer, Myriam Cayre, Joseph Khaldi, Clarisse Bourbon, Isabelle Robles, Gwenaëlle Tardif, Angèle Viola, Rebecca M Pruss, Thierry Bordet, Pascale Durbec
• Journal: Annals of neurology (Ann Neurol) Vol. 71 Issue 2 Pg. 213-26 (Feb 2012) ISSN: 1531-8249 [Electronic] United States
• PMID: 22367994 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Neurological Association.

Chemical References

• Cholestenones
• Monoamine Oxidase Inhibitors
• Cuprizone
• olesoxime

Topics

• Animals
• Cholestenones (therapeutic use)
• Cuprizone (toxicity)
• Demyelinating Diseases (chemically induced, drug therapy)
• Disease Models, Animal
• Magnetic Resonance Imaging
• Mice
• Mice, Inbred C57BL
• Monoamine Oxidase Inhibitors (toxicity)
• Multiple Sclerosis (drug therapy, physiopathology)
• Myelin Sheath (drug effects, physiology)
• Oligodendroglia (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley