Magalon K et al. Olesoxime accelerates myelination and promotes repair in models of demyelination. Anals of Neurology. Feb 2012 DoI: 10.1002/ana.22593 [Epub ahead of print)
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 OPC differentiation and myelin synthesis was tested directly in organotypic slice cultures and OPC-neuron co-cultures. Using naïve animals and different mouse models of demyelination, we morphologically and functionally assessed the effect of the compound on myelination in vivo.
Results: Olesoxine accelerated oligodendrocyte maturation and enhanced myelination in vitro and in vivo in naïve animals during development and also in the adult brain without affecting oligodendrocyte survival or proliferation. In mouse models of demyelination and remyelination, olesoxime favoured the repair process favouring myelin formation with consequent functional improvement.
Interpretation: Our observations support the strategy to promote oligodendrocyte maturation and myelin synthesis to enhance myelin repair and functional recovery. We also provide the proof of concept that olesoxime could be useful for the treatment of demyelinating diseases.
Olesoxime (TRO19622)is a compound in development for motor neuron disease it remains to be seen whether it will be developed for MS. Maybe it could be part of a cockail to help oligodendrocyte maturation, with other agents that promote proliferation. This drug is in trials in humans aimed at motor neuron disease. This drug affects mitochondrial function and so it has the potential to affect nerve damage that could be useful for slowing progression.