Nature 502, 327–332 (2013)

Credit: WILLIAM KIOSSES

Multiple sclerosis (MS) is an autoimmune disorder in which a T cell–mediated immune response in the central nervous system results in the loss of myelin, the protective sheath that insulates nerve fibers. Current MS treatments have managed to tame the early inflammatory responses, limiting myelin losses, but have been less successful in replenishing myelin. To address this gap, Deshmukh et al. performed a high-throughput screen by treating oligodendrocyte precursor cells (OPCs), a myelin progenitor population, with over 100,000 different compounds to search for increases in OPC differentiation into myelin-producing cells. One hit found in the screen was benztropine, which is currently being used to treat Parkinson's disease. Benztropine stimulated the differentiation of OPC cells into myelin-producing cells upon coculture with neurons. Although benztropine has been known to antagonize histamine and dopamine activity, pharmacological experiments suggested that remyelination activity was instead based on the blockade of M1 and M3 muscarinic receptors. The authors tested the therapeutic effects of benztropine on two mouse models with MS-like features. In both cases, benztropine promoted remyelination and alleviated clinical symptoms without altering the overall immune response. As these mouse models recapitulate the major features of human MS, it remains to be seen whether benztropine and/or other analogs can be used in human clinical trials to treat MS.