Novel compounds to promote remyelination in multiple sclerosis

Multiple sclerosis (MS) is a chronic degenerative and debilitating disease of the central nervous system (CNS) characterized by inflammation and demyelination. Despite the improved relapse management provided by immune modulating treatments, progression of the handicap in MS patients remains because of progressive and irreversible axonal degeneration. 


Based on these observations, early neuroprotection and myelin repair strategies should be considered as additional therapeutic requirements for MS patients. Importantly, experimental evidence indicate that new myelin sheaths in MS lesions are formed by oligodendrocyte progenitor cells (OPC) present throughout the adult CNS or newly generated from adult stem cells present in the subventricular zone (SVZ). However this process may be limited because of insufficient OPC recruitment or impaired maturation process. Several growth factors have been shown to affect OPCs survival and proliferation such as platelet-derived growth factor (PDGF), neurotrophin-3 and glial growth factor-2 while insulin-like growth factor (IGF1) and T3 hormone promote their maturation. Mimicking action of theses growth factors with a drug is one of the challenges we addressed.

We previously identified a new class of cholesterol-oxime compounds for their neuroprotective activities. Among these compounds, olesoxime (TRO19622) has been shown to accelerate axon regeneration and remyelination in the peripheral nervous system after sciatic nerve crush