An unmet clinical need: roads to remyelination in MS
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(2019) 1:21
Neurological Research and Practice
REVIEW
Open Access
An unmet clinical need: roads to remyelination in MS Peter Göttle1, Moritz Förster1, Vivien Weyers1, Patrick Küry1, Konrad Rejdak2, Hans-Peter Hartung1 and David Kremer1*
Abstract Background: In the central nervous system (CNS) myelin sheaths stabilize, protect, and electrically insulate axons. However, in demyelinating autoimmune CNS diseases such as multiple sclerosis (MS) these sheaths are destroyed which ultimately leads to neurodegeneration. The currently available immunomodulatory drugs for MS effectively control the (auto)inflammatory facets of the disease but are unable to regenerate myelin by stimulating remyelination via oligodendroglial precursor cells (OPCs). Accordingly, there is broad consensus that the implementation of new regenerative approaches constitutes the prime goal for future MS pharmacotherapy. Main text: Of note, recent years have seen several promising clinical studies investigating the potential of substances and monoclonal antibodies such as, for instance, clemastine, opicinumab, biotin, simvastatin, quetiapin and anti-GNbAC1. However, beyond these agents which have often been re-purposed from other medical indications there is a multitude of further molecules influencing OPC homeostasis. Here, we therefore discuss these possibly beneficial regulators of OPC differentiation and assess their potential as new pharmacological targets for myelin repair in MS. Conclusion: Remyelination remains the most important therapeutic treatment goal in MS in order to improve clinical deficits and to avert neurodegeneration. The promising molecules presented in this review have the potential to promote remyelination and therefore warrant further translational and clinical research. Keywords: Remyelination, Myelin, Neurodegeneration, Oligodendrocyte, Therapy, Multiple sclerosis
Introduction Axonal myelin sheaths enable saltatory signal transduction which accelerates information processing 20–100-fold. However, many diseases of the central nervous system (CNS) such as multiple sclerosis (MS) harm or destroy myelin sheaths and the myelin-producing oligodendrocytes resulting in demyelination. MS is an autoimmune inflammatory CNS disease of yet unclear etiology [75, 91]. Its most common clinical course is the relapsing subtype (RMS) which can manifest itself in a plethora of acute clinical symptoms (i.e. relapses) ranging from paresthesias to ataxia or even motor weakness. Most RMS cases ultimately transform into (secondary) progressive MS (PMS) where neurodegeneration outweighs inflammation. Even though there is evidence that adult oligodendrocyte can contribute to myelin repair in the adult CNS [18, 103], * Correspondence: [email protected] 1 Department of Neurology, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany Full list of author information is available at the end of the article
remyelination is thought to be mostly mediated by an ubiquitous pool of so-called oligodendroglia
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