An unmet clinical need: roads to remyelination in MS.
Multiple sclerosis
Myelin
Neurodegeneration
Oligodendrocyte
Remyelination
Therapy
Journal
Neurological research and practice
ISSN: 2524-3489
Titre abrégé: Neurol Res Pract
Pays: England
ID NLM: 101767802
Informations de publication
Date de publication:
2019
2019
Historique:
received:
11
03
2019
accepted:
14
05
2019
entrez:
16
12
2020
pubmed:
8
7
2019
medline:
8
7
2019
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
METHODS
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
CONCLUSIONS
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.
Identifiants
pubmed: 33324887
doi: 10.1186/s42466-019-0026-0
pii: 26
pmc: PMC7650135
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
21Informations de copyright
© The Author(s) 2019.
Déclaration de conflit d'intérêts
Competing interestsPG and PK performed consultancy work for GeNeuro. HPH received consultancy fees and fees for serving on steering or data monitoring committees and adboards from Bayer Healthcare, Biogen, GeNeuro, Genzyme, MedDay, Merck, Novartis, Celgene Receptos, Roche, Teva with approval by the Rector of Heinrich-Heine-University. DK received travel grants from GeNeuro and Merck, refund of congress participation fees from GeNeuro, Merck, Servier, consulting fees from Grifols, payment for lectures from Grifols and support for research projects from Teva. MF, VW and KR declare that they have no competing interests.
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