Zuroff Leah, Farkhondeh Vista, Bove Riley, Green Ari J
Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
UC Davis School of Medicine, University of California Davis, Sacramento, CA, USA.
Drugs. 2025 Sep 16. doi: 10.1007/s40265-025-02212-x.
Despite major advances in multiple sclerosis (MS) treatment, disability accumulation independent of relapse activity remains a significant challenge. Chronic demyelination is a key driver of neurodegeneration and disease progression, highlighting remyelination as a promising therapeutic strategy. Collective evidence from several phase II clinical trials now indicates that remyelination is feasible in patients with MS. However, several drug development programs have yielded less robust responses than anticipated, which has limited translation of therapies into clinical practice. This underscores the need for refined trial methodologies, including careful selection of patient populations, validation of biomarkers, and implementation of functional outcomes that accurately capture remyelination effects. In this review, we summarize the current understanding of remyelination mechanisms, assess the therapeutic landscape, and discuss strategies to improve clinical trial design. Addressing key questions-such as the optimal timing, patient selection, and methods of measurement-will be crucial for advancing the field and ushering in a new wave of MS therapeutics.
尽管多发性硬化症（MS）治疗取得了重大进展，但与复发活动无关的残疾累积仍然是一项重大挑战。慢性脱髓鞘是神经退行性变和疾病进展的关键驱动因素，这凸显了髓鞘再生作为一种有前景的治疗策略的重要性。来自多项II期临床试验的综合证据表明，MS患者的髓鞘再生是可行的。然而，一些药物研发项目产生的反应不如预期强烈，这限制了治疗方法向临床实践的转化。这突出了改进试验方法的必要性，包括仔细选择患者群体、验证生物标志物以及实施能够准确捕捉髓鞘再生效果的功能结局指标。在本综述中，我们总结了目前对髓鞘再生机制的理解，评估了治疗前景，并讨论了改进临床试验设计的策略。解决诸如最佳时机、患者选择和测量方法等关键问题对于推动该领域发展以及引领MS治疗的新一波浪潮至关重要。
