Ospemifene, a Selective Estrogen Receptor Modulator, Enhances Oligodendrocyte Myelination and Preserves...

Insufficient myelinogenesis following central nervous system (CNS) injuries is a well-documented pathological feature in various diseases, such as white matter injury (WMI) and multiple sclerosis (MS). Repurposing FDA-approved drugs capable of promoting oligodendrocytes (OLs) differentiation represents a realistic and feasible approach for myelin repair and functional recovery. In this study, we report that ospemifene, an FDA-approved selective estrogen receptor modulator (SERM), significantly promotes the differentiation of purified mouse oligodendrocyte precursor cells (OPCs) both in cultures and on nanofibers. In neonatal mice subjected to hypoxia, ospemifene prevented hypoxia-induced myelin deficits in the developing central nervous system (CNS) and preserved neurofunctions in young adolescents, likely due to its promyelination potency. To assess the impact in demyelination models, we utilized the experimental autoimmune encephalomyelitis (EAE) mouse model, and ospemifene treatment alleviated functional deterioration in a dose-dependent manner and benefited myelin regeneration. To confirm the effect on remyelination, toxin-induced demyelination mice, injected with lysophosphatidylcholine into the corpus callosum, were treated with ospemifene. This treatment increased newly generated myelin sheaths in the lesions, confirming its promyelinogenesis effect. Together, our findings suggest that ospemifene is a promising treatment option for demyelinating diseases.