Emerging myelin repair agents in preclinical and early clinical development for the treatment of multiple sclerosis

Abstract

ABSTRACT Introduction Remyelination is a highly effective regenerative process that can restore axon function, prevent axonal loss, and reverse clinical deficits after demyelination. Hence, the promotion of remyelination is a logical goal in patients with multiple sclerosis (MS) in which remyelination is often insufficient. However, despite great progress regarding the development of immunomodulatory therapies for MS and an abundance of promising evidence from preclinical experiments so far, no therapy has convincingly demonstrated clinically significant remyelination properties. Therefore, enhancing myelin repair is an urgent and unmet need in MS. Areas covered We searched clinicaltrials.gov and pubmed.ncbi.nlm.nih.gov and focused on therapeutic agents in development from the preclinical stage to clinical phase II. We selected agents for which data are available from in vitro experiments and at least one toxic demyelination animal model that reached at least phase I in clinical development in MS patients. Expert opinion The evidence to promote remyelination is very promising for several agents, some of which possess anti-muscarinergic properties. Since remyelination is a complex process that involves various coordinated steps, a combination of different therapeutic approaches addressing different aspects of this regenerative mechanism may be reasonable. Furthermore, suitable surrogate markers of remyelination are necessary for proof-of-concept clinical trials.