An unmet clinical need: roads to remyelination in MS

In the central nervous system (CNS) myelin sheaths stabilize, protect, and electrically insulate axons. However, in demyelinating autoimmune CNS diseases such as multiple sclerosis (MS) these sheaths are destroyed which ultimately leads to neurodegeneration. The currently available immunomodulatory drugs for MS effectively control the (auto)inflammatory facets of the disease but are unable to regenerate myelin by stimulating remyelination via oligodendroglial precursor cells (OPCs). Accordingly, there is broad consensus that the implementation of new regenerative approaches constitutes the prime goal for future MS pharmacotherapy.

Of note, recent years have seen several promising clinical studies investigating the potential of substances and monoclonal antibodies such as, for instance, clemastine, opicinumab, biotin, simvastatin, quetiapin and anti-GNbAC1. However, beyond these agents which have often been re-purposed from other medical indications there is a multitude of further molecules influencing OPC homeostasis. Here, we therefore discuss these possibly beneficial regulators of OPC differentiation and assess their potential as new pharmacological targets for myelin repair in MS.

Remyelination remains the most important therapeutic treatment goal in MS in order to improve clinical deficits and to avert neurodegeneration. The promising molecules presented in this review have the potential to promote remyelination and therefore warrant further translational and clinical research.