TY - JOUR
T1 - Remyelination therapies for multiple sclerosis
T2 - optimizing translation from animal models into clinical trials
AU - Sutiwisesak, Rujapope
AU - Burns, Terry C.
AU - Rodriguez, Moses
AU - Warrington, Arthur E.
N1 - Funding Information:
R Sutiwisesak received financial support from the Faculty of Medicine Siriraj Hospital, Mahidol University. AE Warrington was supported by Regenerative Medicine Minnesota RMM 091718 TR 011 and the Robert and Arlene Kogod Center on Aging. TC Burns was supported by NIH K12 NRDCP, NINDS NS19770, the Minnesota Partnership for Biotechnology and Genomics, Mayo Clinic Center for Regenerative Medicine, Lucius & Terrie McKelvey, Regenerative Medicine Minnesota, Humor to Fight the Tumor, Brains Together for the Cure and the Robert and Arlene Kogod Center on Aging.
Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - Introduction: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system (CNS). Demyelination, the main pathology in MS, contributes to clinical symptoms and long-term neurological deficits if left untreated. Remyelination, the natural repair of damaged myelin by cells of the oligodendrocyte lineage, occurs in MS, but eventually fails in most patients as they age. Encouraging timely remyelination can restore axon conduction and minimize deficits. Areas covered: We discuss and correlate human MS pathology with animal models, propose methods to deplete resident oligodendrocyte progenitor cells (OPCs) to determine whether mature oligodendrocytes support remyelination, and review remyelinating agents, mechanisms of action, and available clinical trial data. Expert opinion: The heterogeneity of human MS may limit successful translation of many candidate remyelinating agents; some patients lack the biological targets necessary to leverage current approaches. Development of therapeutics for remyelination has concentrated almost exclusively on mobilization of innate OPCs. However, mature oligodendrocytes appear an important contributor to remyelination in humans. Limiting the contribution of OPC mediated repair in models of MS would allow the evaluation of remyelination-promoting agents on mature oligodendrocytes. Among remyelinating reagents reviewed, only rHIgM22 targets both OPCs and mature oligodendrocytes.
AB - Introduction: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system (CNS). Demyelination, the main pathology in MS, contributes to clinical symptoms and long-term neurological deficits if left untreated. Remyelination, the natural repair of damaged myelin by cells of the oligodendrocyte lineage, occurs in MS, but eventually fails in most patients as they age. Encouraging timely remyelination can restore axon conduction and minimize deficits. Areas covered: We discuss and correlate human MS pathology with animal models, propose methods to deplete resident oligodendrocyte progenitor cells (OPCs) to determine whether mature oligodendrocytes support remyelination, and review remyelinating agents, mechanisms of action, and available clinical trial data. Expert opinion: The heterogeneity of human MS may limit successful translation of many candidate remyelinating agents; some patients lack the biological targets necessary to leverage current approaches. Development of therapeutics for remyelination has concentrated almost exclusively on mobilization of innate OPCs. However, mature oligodendrocytes appear an important contributor to remyelination in humans. Limiting the contribution of OPC mediated repair in models of MS would allow the evaluation of remyelination-promoting agents on mature oligodendrocytes. Among remyelinating reagents reviewed, only rHIgM22 targets both OPCs and mature oligodendrocytes.
KW - GSK239512
KW - Myelin
KW - Opicinumab
KW - Remyelination
KW - clemastine
KW - clinical trials
KW - multiple sclerosis
KW - olesoxime
KW - oligodendrocyte
KW - progenitor cells
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U2 - 10.1080/13543784.2021.1942840
DO - 10.1080/13543784.2021.1942840
M3 - Review article
C2 - 34126015
AN - SCOPUS:85108839505
VL - 30
SP - 857
EP - 876
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
SN - 1354-3784
IS - 8
ER -