title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Developmental Biology Institute of Marseille-Luminy, French National Center for Scientific Research Joint Research Unit, Universite de la Mediterranee, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Magalon
authors.forename: Celine
authors.initials: C
authors.lastname: Zimmer
authors.forename: Myriam
authors.initials: M
authors.lastname: Cayre
authors.forename: Joseph
authors.initials: J
authors.lastname: Khaldi
authors.forename: Clarisse
authors.initials: C
authors.lastname: Bourbon
authors.forename: Isabelle
authors.initials: I
authors.lastname: Robles
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Tardif
authors.forename: Angèle
authors.initials: A
authors.lastname: Viola
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Pruss
authors.forename: Thierry
authors.initials: T
authors.lastname: Bordet
authors.forename: Pascale
authors.initials: P
authors.lastname: Durbec
mesh_terms: D000818:Animals; D002783:Cholestenones / Q000627:therapeutic use*; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D009186:Myelin Sheath / Q000187:drug effects* / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002783:Cholestenones; D008996:Monoamine Oxidase Inhibitors; D003471:Cuprizone; C522838:olesoxime