Multiple Sclerosis Journal 1–9 DOI: 10.1177/ 1352458514566419 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav MULTIPLE SCLEROSIS MSJ JOURNAL http://msj.sagepub.com 1 Multiple sclerosis (MS)—a disease with remyelination failure MS, first described by Jean-Martin Charcot almost 150 years ago, 1 is a chronic inflammatory disease of the central nervous system (CNS). As tissue damage in MS was solely considered to be the result of an auto- immune inflammatory CNS process, it is hardly sur- prising that therapies developed over the course of the last 20 years have mainly focused on the immune sys- tem and, more specifically, on the modulation of immune cell behavior. Even though the currently available MS drugs are reliable, constantly improv- ing, 2 very effective in MS with relapses, and able to significantly reduce long-term disability in MS patients, 3 they have only a limited effect on the pro- gressive disease course without additional inflamma- tory relapses. 4 As neuroarchitectural damage caused during disease relapses accumulates over time and results in increasing patient disability, it is critical to develop new therapies aiming at the regenerative mechanisms of MS pathogenesis. Neurological disability during relapsing–remitting mul- tiple sclerosis (RRMS) occurs in reversible episodes driven primarily by focal inflammatory demyelination, which destroys myelin, myelin-forming cells (oligoden- drocytes), and axons. 5 Untreated relapses usually last no more than a few months, after which the patient typi- cally regains neurological function. Remyelination, accompanied by resolution of the inflammation and reorganization of axonal sodium channels on demyeli- nated axons, helps restore axonal conduction and con- tributes to the clinical recovery or remission. 6 This remyelination during early disease is extensive in some MS patients but declines during the progressive disease course. 7,8 During this progressive phase of the disease, where acute inflammatory relapses are scarce with increasing loss of neuronal function, exogenous stimu- lation of endogenous remyelination would potentially have the greatest impact. Oligodendroglial precursor cells (OPCs) as a source for remyelination Current research on the treatment of MS is directed at three major goals: preventing the development of new demyelinating lesions, protecting demyelinated axons from degeneration, and promoting remyelination. Phases of remyelination occur frequently during the RRMS disease course and are probably most relevant Promoting remyelination in multiple sclerosis: Current drugs and future prospects David Kremer, Patrick Küry and Ranjan Dutta Abstract: Myelin destruction due to inflammatory oligodendrocyte cell damage or death in conjunction with axonal degeneration are among the major histopathological hallmarks of multiple sclerosis (MS). The majority of available immunomodulatory medications for MS are approved for relapsing–remitting (RR) MS, for which they reduce relapse rate, MRI measures of inflammation, and the accumulation of disability. These medications are, however, of little benefit during progressive MS where axonal degen- eration following demyelination outweighs inflammation. This has sparked great interest in the develop- ment of new remyelination therapies aimed at reversing the neurodegenerative damage observed in this disease. Remyelination as a result of oligodendrocyte production from oligodendrocyte precursor cells (OPCs) is considered a promising potential target for the treatment of all stages of MS. In this review we present an overview of a) approved medications (some of them FDA-and EMA-approved for other dis- eases) with a proposed role in regeneration, b) regenerative treatments under investigation in clinical tri- als, and c) promising future therapeutic approaches aiming specifically at facilitating endogenous repair. Keywords: Multiple sclerosis, therapy, trials, remyelination Date received: 10 November 2014; revised: 17 November 2014; accepted: 27 November 2014 Correspondence to: Ranjan Dutta Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., NC-30, Cleveland, OH 44195, USA. duttar@ccf.org Patrick Küry Department of Neurology, Medical Faculty, University of Düsseldorf, Germany Ranjan Dutta Department of Neurosciences, Lerner Research Institute, USA David Kremer Department of Neurology, Medical Faculty, University of Düsseldorf, Germany/Department of Neurosciences, Lerner Research Institute, USA 566419MSJ 0 0 10.1177/1352458514566419Multiple Sclerosis JournalD Kremer, P Küry research-article 2015 Topical Review by guest on September 24, 2016 msj.sagepub.com Downloaded from