Remyelinating the adult central nervous system: Repairing injury in MS

Multiple Sclerosis is a debilitating neurodegnerative disease of the central nervous system in which the immune system targets and destroys myelin sheaths surrounding axons. Progressive and permanent neurological disability in the disease is caused by the ultimate loss of the underlying axons themselves. Nearly a dozen FDA-approved therapies exist to help reduce the inflammation that contributes to immune mediated injury or prevent the influx of immune cells from peripheral circulation into the CNS. However, to date there are no therapies capable of protecting axon loss and/or regenerating lost myelin. There are compelling reasons to think that maintenance or restoration of myelin integrity would help with protection of axons from loss and injury. Myelin in the CNS is an extension of the plasma membrane from mature oligodendrocytes - a specialized cell type whose principal purpose is to provide the myelin needed to ensheath axons. The precursor cell for oligodendrocytes known as OPCs are tiled throughout the CNS, but they don't appear to adequately differentiate into mature oligodendrocytes capable of restoring myelination to denuded axons. This talk will discuss the use of a novel high throughput screen for the identification of small molecules with the capacity to induce oligodendrocyte differentiation and myelin wrapping. It will also discuss the validation of the "hits" from this screening assay and the rapid introduction of these therapeutic targets to patients including the selection of targets focusing on mechanism of action and BBB penetration. This will include discussion of the importance of development of clinical trial outcomes for the advancement of successful therapeutic programs in neuroprotection.