Wooliscroft Lindsey, Silbermann Elizabeth, Cameron Michelle, Bourdette Dennis
Department of Neurology, Oregon Health & Science University, L226, 3181 S.W. Sam Jackson Park Road, Portland, OR, 97239, USA.
Department of Veterans Affairs Portland Health Care System, Portland, OR, 97239, USA.
Curr Treat Options Neurol. 2019 Jun 28;21(7):34. doi: 10.1007/s11940-019-0574-1.
While there are a growing number of therapies targeting relapse prevention in multiple sclerosis (MS), there are no approved therapies promoting remyelination. Understanding endogenous myelin formation, remyelination strategies, pre-clinical models, and clinical outcomes is essential to the interpretation of current and future clinical trials of remyelinating agents.
Several recent clinical trials of remyelination therapies, including opicinumab, clemastine, and GSK239512, showed negative or modest results. These results could highlight challenges translating pre-clinical studies into subjects with MS and current strategies to measure remyelination. Current approaches to remyelination include (1) blocking inhibitors of remyelination, (2) improving the clearance of myelin debris, (3) increasing the number of oligodendrocyte precursor cells (OPCs), and (4) stimulating OPC differentiation. To date, no therapies have led to robust remyelination. Future efforts to promote remyelination will likely require a combination of these mechanistic strategies.
虽然针对多发性硬化症（MS）预防复发的疗法越来越多，但尚无获批的促进髓鞘再生的疗法。了解内源性髓鞘形成、髓鞘再生策略、临床前模型和临床结果对于解释当前及未来髓鞘再生剂的临床试验至关重要。
最近几项髓鞘再生疗法的临床试验，包括奥匹珠单抗、氯马斯汀和GSK239512，结果均为阴性或效果一般。这些结果可能凸显了将临床前研究转化至MS患者以及当前测量髓鞘再生策略方面所面临的挑战。当前的髓鞘再生方法包括：（1）阻断髓鞘再生抑制剂；（2）改善髓鞘碎片清除；（3）增加少突胶质前体细胞（OPC）数量；（4）刺激OPC分化。迄今为止，尚无疗法能实现显著的髓鞘再生。未来促进髓鞘再生的努力可能需要综合运用这些机制策略。
