Ipratropium Promotes Oligodendrocyte Progenitor Cells Differentiation
and Accelerates Recovery in Adult Demyelinated Mice
Abstract
As potentially the most common cause of neurological disability in young
adults, multiple sclerosis (MS) is an inflammatory demyelinating disease
of the central nervous system (CNS) that results in chronic progressive
disability for most patients. None of existing therapeutic agents could
effectively inhibit the chronic progression, primarily due to their
incapacity to stop or reverse remyelination failure in demyelinating
lesions. Identifying compounds that promote remyelination represents a
major challenge in the development of therapeutics for MS. Based on the
drug-repurposing strategy and signature mapping approach, we employed
the expanded Connectivity Map (CMap) and in cell western analysis to
efficiently screen potential compounds. Ipratropium was ultimately
selected and further validated for the efficacy in modulating OPCs
differentiation in vitro and myelin regeneration in the demyelinating
models. Collectively, our results provide a novel high-throughput
screening strategy for potential regenerative therapeutics in MS.