GABAB receptor agonist baclofen promotes central nervous system remyelination

Promoting remyelination is considered as a potential neurorepair strategy to prevent/limit the development of permanent neurological disability in patients with multiple sclerosis (MS). To this end, a number of clinical trials are investigating the potential of existing drugs to enhance oligodendrocyte progenitor cell (OPC) differentiation, a process that fails in chronic MS lesions. We previously reported that oligodendroglia express GABAB receptors (GABABRs) both in vitro and in vivo, and that GABABR‐mediated signaling enhances OPC differentiation and myelin protein expression in vitro. Our goal here was to evaluate the pro‐remyelinating potential of GABABR agonist baclofen (Bac), a clinically approved drug to treat spasticity in patients with MS. We first demonstrated that Bac increases myelin protein production in lysolecithin (LPC)‐treated cerebellar slices. Importantly, Bac administration to adult mice following induction of demyelination by LPC injection in the spinal cord resulted in enhanced OPC differentiation and remyelination. Thus, our results suggest that Bac repurposing should be considered as a potential therapeutic strategy to stimulate remyelination in patients with MS. Main Points Baclofen enhances myelin protein synthesis in cerebellar organotypic cultures demyelinated with lysolecithin (LPC). Baclofen increases oligodendrocyte progenitor cell (OPC) differentiation and remyelination in demyelinated lesions from spinal cord in adult mice.