Targeting Stem Cells to Enhance Remyelination in the Treatment of Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease in which the myelin sheath that insulates neurons is destroyed, resulting in loss of proper neuronal function. Existing treatments for MS are based on strategies that suppress the immune response. While these drugs do provide benefit by reducing relapses and delaying progression (but have significant side effects), the disease invariably progresses. We are pursuing an alternative therapy aimed at regeneration of the myelin sheath through drugs that act on an endogenous stem cell population in the central nervous system termed oligodendrocyte precursor cells (OPCs). Remission in MS is largely dependent upon OPCs migrating to sites of injury and subsequently differentiating into oligodendrocytes – the cells that synthesize myelin and are capable of neuronal repair. Previous studies indicate that in progressive MS, OPCs are abundantly present at sites of damage but fail to differentiate to oligodendrocytes. As such, drug-like molecules capable of inducing OPC differentiation should have significant potential, used alone or in combination with existing immunomodulatory agents, for the treatment of MS. The objective of this project is to identify a development candidate (DC) for the treatment of multiple sclerosis (MS) that functions by directly stimulating the differentiation of the adult stem cells required for remyelination.