Approaches to Remyelination Therapies in Multiple Sclerosis
Purpose of review
While there are a growing number of therapies targeting relapse prevention in multiple sclerosis (MS), there are no approved therapies promoting remyelination. Understanding endogenous myelin formation, remyelination strategies, pre-clinical models, and clinical outcomes is essential to the interpretation of current and future clinical trials of remyelinating agents.
Several recent clinical trials of remyelination therapies, including opicinumab, clemastine, and GSK239512, showed negative or modest results. These results could highlight challenges translating pre-clinical studies into subjects with MS and current strategies to measure remyelination.
Current approaches to remyelination include (1) blocking inhibitors of remyelination, (2) improving the clearance of myelin debris, (3) increasing the number of oligodendrocyte precursor cells (OPCs), and (4) stimulating OPC differentiation. To date, no therapies have led to robust remyelination. Future efforts to promote remyelination will likely require a combination of these mechanistic strategies.
KeywordsRemyelination Multiple sclerosis Oligodendrocyte precursor cell Opicinumab Clemastine GSK239512
Dr. Wooliscroft would like to thank the Veterans Administration MS Center of Excellence-West for their support in her fellowship. Dr. Silbermann would like to thank the National MS Society for their support of her fellowship through a Sylvia Lawry Award.
Compliance with Ethical Standards
Conflict of Interest
Lindsey Wooliscroft and Elizabeth Silbermann each declare no potential conflicts of interest. Michelle Cameron reports consulting fees from Adamas Pharmaceuticals and Greenwich Biosciences outside the submitted work. Dennis Bourdette reports consultancy for reviewing patient medical records and providing opinion on treatments for Magellan Health Care and Best Doctors Inc. He also served as an expert witness on MS for the US Department of Justice, reports a bench research grant and collaborative center award from the National MS Society, and reports a founder’s stock valued at $1000 from Llama Therapeutics.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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