Promoting remyelination in multiple sclerosis-recent advances

Abstract

We review the current state of knowledge of remyelination in multiple sclerosis (MS), concentrating on advances in the understanding of the pathology and the regenerative response, and we summarise progress on the development of new therapies to enhance remyelination aimed at reducing progressive accumulation of disability in MS. We discuss key target pathways identified in experimental models, as although most identified targets have not yet progressed to the stage of being tested in human clinical trials, they may provide treatment strategies for demyelinating diseases in the future. Finally, we discuss some of the problems associated with testing this class of drugs, where they might fit into the therapeutic arsenal and the gaps in our knowledge.

Fig. 1

Major steps required for remyelination. For successful remyelination, oligodendrocyte precursor cells need to be recruited to the lesion site and then differentiate into myelinating oligodendrocytes. This is a very intricate process that can fail if not regulated effectively

Fig. 2

Selected factors that influence remyelination and their mechanism of action. Several factors/signalling pathways, which positively (green) or negatively (red) influence remyelination by altering known necessary steps during the remyelination process have already been identified. BMP bone morphogenic proteins, PDGF platelet-derived growth factor