Drug discovery for remyelination and treatment of MS

Glia constitute the majority of the cells in our nervous system, yet there are currently no drugs that target glia for the treatment of disease. Given ongoing discoveries of the many roles of glia in numerous diseases of the nervous system, this is likely to change in years to come. Here we focus on the possibility that targeting the oligodendrocyte lineage to promote regeneration of myelin (remyelination) represents a therapeutic strategy for the treatment of the demyelinating disease multiple sclerosis, MS. We discuss how hypothesis driven studies have identified multiple targets and pathways that can be manipulated to promote remyelination in vivo, and how this work has led to the first ever remyelination clinical trials. We also highlight how recent chemical discovery screens have identified a host of small molecule compounds that promote oligodendrocyte differentiation in vitro. Some of these compounds have also been shown to promote myelin regeneration in vivo, with one already being trialled in humans. Promoting oligodendrocyte differentiation and remyelination represents just one potential strategy for the treatment of MS. The pathology of MS is complex, and its complete amelioration may require targeting multiple biological processes in parallel. Therefore, we present an overview of new technologies and models for phenotypic analyses and screening that can be exploited to study complex cell-cell interactions in in vitro and in vivo systems. Such technological platforms will provide insight into fundamental mechanisms and increase capacities for drug-discovery of relevance to glia and currently intractable disorders of the CNS.