New targets and therapeutics for neuroprotection, remyelination and repair in multiple sclerosis

ABSTRACT

Introduction

Immunotherapies for multiple sclerosis (MS) significantly decrease the risk of new relapses. However, the chronic compartmentalized inflammation and neurodegeneration that define progressive MS are not prevented by these therapies and so significant damage to the brain and spinal cord and resulting disability ensues. Hence, the possibility of combining current immunotherapies with neuroprotective, remyelinating or regenerative therapies should be pursued.

Areas covered

This article sheds light on neuroprotective, remyelination and neurorepair strategies for MS, the numerous mechanisms for therapeutic targeting and the new candidates for combination therapies. We searched PubMed for articles with the terms, ‘neuroprotection’, remyelination’ or ‘regeneration’ and ‘therapies’ or ‘drugs’ and ‘Multiple Sclerosis’.

Expert opinion

An enriched understanding of the neurobiology and molecular changes that are activated by inflammatory CNS damage will provide new opportunities for the identification of neuroprotective, remyelinating and regenerative therapies. Success will depend on the improvement of CNS drug delivery, the identification of new predictive biomarkers, the optimization of clinical trials by assessment of the damage to the visual pathway and the testing of novel therapies in acute optic neuritis.

KEYWORDS:

• Multiple Sclerosis
• neuroprotection
• remyelination
• regeneration
• neurorepair
• therapies
• drug

Article Highlights

• The prevention of disabilities associated with MS progression is a significant unmet need for patients.

• Neuroprotection, remyelination and regeneration therapies are being pursued, along with immunomodulatory drugs and combination therapies.

• Many targets have been proposed for neuroprotection, but their efficacy in clinical trials has not been proven. An enhanced understanding of neurobiology and novel technologies for CNS penetration pave the way for the development of effective therapies to prevent CNS damage.

• Remyelinating therapies have been improved by our understanding of oligodendrocytes and their precursors.

• The assessment of the damage to the visual pathway during clinical trials and the testing of novel therapies for acute optic neuritis offers opportunities for the development of new therapeutics.

This box summarizes key points contained in the article.

Acknowledgments

We would like to thank Mark Sefton for the English revision of the manuscript.

Declaration of interest

P Villoslada hold stock and stock options, and has received consultancy fees from Bionure Farma SL, Spiral Therapeutics Inc, Health Engineering SL, QMenta Inc, Attune Neurosciences Inc, CLight Inc and NeuroPrex Inc. PV hold patent rights on BN201 and Methylthioadenosine for the treatment of MS and other brain diseases. L Steinman is a founder of Tolerion, Atreca, Neurocrine, and 180 Therapeutics, where he is a shareholder, and a patent holder for antigen tolerization for MS and other autoimmune diseases. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has served as a Biogen, Merck Serono, Novartis, Roche, Sanofi/Genzyme and Teva Advisory Board Member and has received congress and travel/accommodation expense compensations or speaker honoraria from Biogen, Merck, Mylan, Novartis, Sanofi/Genzyme, Teva and Fondazione Italiana Sclerosi Multipla (FISM). His/her institutions have received research grants from Novartis. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

P Villoslada has received research grants from the European Commission, the Instituto de Salud Carlos III, the GAEM foundation, the Guthy Jackson Foundation, and the MaratoTV3 foundation. L Steinman has received research grants from the NIH, the Muscular Dystrophy Association Grant and the National Multiple Sclerosis Society.