Remyelination therapies: a new direction and challenge in multiple sclerosis

Key Points People with multiple sclerosis exhibit variable degrees of remyelination. Individuals with greater capacity to remyelinate seem to have less clinical disability, thereby fuelling the research to find remyelination therapeutics for multiple sclerosis. The biology of remyelination and its similarities and differences from developmental myelination are discussed. Many pro-remyelinating therapeutics have been identified from experimental models. Early phase clinical trials with potential pro-remyelinating therapeutics are in progress. Many challenges remain on how best to perform clinical trials of potential pro-remyelinating medications for multiple sclerosis. Restoring damaged myelin could reverse the neurological effects observed in patients with multiple sclerosis. In this Review, Yong and colleagues discuss the progress made in remyelinating therapies, including novel and potential repurposed agents, and highlight the challenges in preclinical and clinical development for such drugs. Multiple sclerosis is characterized by inflammatory activity that results in destruction of the myelin sheaths that enwrap axons. The currently available medications for multiple sclerosis are predominantly immune-modulating and do not directly promote repair. White matter regeneration, or remyelination, is a new and exciting potential approach to treating multiple sclerosis, as remyelination repairs the damaged regions of the central nervous system. A wealth of new strategies in animal models that promote remyelination, including the repopulation of oligodendrocytes that produce myelin, has led to several clinical trials to test new reparative therapies. In this Review, we highlight the biology of, and obstacles to, remyelination. We address new strategies to improve remyelination in preclinical models, highlight the therapies that are currently undergoing clinical trials and discuss the challenges of objectively measuring remyelination in trials of repair in multiple sclerosis.