Clinical implications of myelin regeneration in the central nervous system

ABSTRACT

Introduction: Amongst strategies to repair the brain, myelin repair offers genuine cause for optimism. Myelin, which sheaths most axons in the central nervous system (CNS), is vital for normal neurological function, as demonstrated by the functional deficits that accrue when it is absent in a range of debilitating myelin diseases. Following demyelination, post-mortem and imaging studies have shown that extensive regeneration of myelin is possible in the human brain. Over recent decades preclinical research has given us a strong understanding of the biology of myelin regeneration, opening up several exciting therapeutic opportunities that are on the cusp of clinical translation.

Areas covered: This review discusses diseases that compromise the function of myelin, the endogenous capacity of the CNS to regenerate myelin, and why this sometimes fails. We then outline the extensive progress that has been made towards therapies that promote the regeneration of myelin.

Expert commentary: Finally, a commentary on the first examples of these therapies to reach human patients and the evidence base that supports them, giving our opinion on where attention should be focused going forward is provided.

KEYWORDS:

• Myelin
• regeneration
• remyelination
• repair
• oligodendrocyte progenitor cell
• oligodendrocyte
• ageing
• inflammation
• imaging

Declaration of interest

RJM Franklin is an investigator in a clinical trial for bexarotene in multiple sclerosis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

RJMF’s lab is supported by a core support grant from the Wellcome Trust and Medical Research Council to the Wellcome Trust StemCell Institute. The authors would also like to acknowledge the support of the UK MS Society, The Jean Shanks Foundation, and MedImmune.