Abstract：
BACKGROUND: Amelioration of disability in multiple sclerosis requires the development of complementary therapies that target neurodegeneration and promote repair. Remyelination is a promising neuroprotective strategy that may protect axons from damage and subsequent neurodegeneration.
METHODS: A review of key literature plus additional targeted search of PubMed and Google Scholar was conducted.
RESULTS: There has been a rapid expansion of clinical trials studying putative remyelinating candidates, but further growth of the field is limited by the lack of consensus on key aspects of trial design. We have not yet defined the ideal study population, duration of therapy, or the appropriate outcome measures to detect remyelination in humans. The varied natural history of multiple sclerosis, coupled with the short time frame of phase II clinical trials, requires that we develop and validate biomarkers of remyelination that can serve as surrogate endpoints in clinical trials.
CONCLUSIONS: We propose that the visual system may be the most well-suited and validated model for the study potential remyelinating agents. In this review, we discuss the pathophysiology of demyelination and summarize the current clinical trial landscape of remyelinating agents. We present some of the challenges in the study of remyelinating agents and discuss current potential biomarkers of remyelination and repair, emphasizing both established and emerging visual outcome measures.
METHODS: A review of key literature plus additional targeted search of PubMed and Google Scholar was conducted.
RESULTS: There has been a rapid expansion of clinical trials studying putative remyelinating candidates, but further growth of the field is limited by the lack of consensus on key aspects of trial design. We have not yet defined the ideal study population, duration of therapy, or the appropriate outcome measures to detect remyelination in humans. The varied natural history of multiple sclerosis, coupled with the short time frame of phase II clinical trials, requires that we develop and validate biomarkers of remyelination that can serve as surrogate endpoints in clinical trials.
CONCLUSIONS: We propose that the visual system may be the most well-suited and validated model for the study potential remyelinating agents. In this review, we discuss the pathophysiology of demyelination and summarize the current clinical trial landscape of remyelinating agents. We present some of the challenges in the study of remyelinating agents and discuss current potential biomarkers of remyelination and repair, emphasizing both established and emerging visual outcome measures.
摘要：
背景：改善多发性硬化症的残疾需要开发针对神经变性并促进修复的补充疗法。髓鞘再生是一种有前途的神经保护策略，可以保护轴突免受损伤和随后的神经变性。
方法：对关键文献进行了回顾，并对PubMed和GoogleScholar进行了额外的针对性搜索。
结果：研究推定的髓鞘再生候选物的临床试验迅速扩大，但由于在试验设计的关键方面缺乏共识,该领域的进一步发展受到限制.我们还没有定义理想的研究人群，治疗持续时间，或适当的结果措施来检测人类的髓鞘再生。多发性硬化症的不同自然史，再加上II期临床试验的短时限，需要我们开发和验证髓鞘再生的生物标志物，这些生物标志物可以在临床试验中作为替代终点。
结论：我们认为视觉系统可能是研究潜在髓鞘再生剂的最适合和验证的模型。在这次审查中,我们讨论了脱髓鞘的病理生理学，并总结了当前髓鞘再生剂的临床试验情况。我们提出了髓鞘再生剂研究中的一些挑战，并讨论了当前髓鞘再生和修复的潜在生物标志物。强调既定和新兴的视觉结果措施。
方法：对关键文献进行了回顾，并对PubMed和GoogleScholar进行了额外的针对性搜索。
结果：研究推定的髓鞘再生候选物的临床试验迅速扩大，但由于在试验设计的关键方面缺乏共识,该领域的进一步发展受到限制.我们还没有定义理想的研究人群，治疗持续时间，或适当的结果措施来检测人类的髓鞘再生。多发性硬化症的不同自然史，再加上II期临床试验的短时限，需要我们开发和验证髓鞘再生的生物标志物，这些生物标志物可以在临床试验中作为替代终点。
结论：我们认为视觉系统可能是研究潜在髓鞘再生剂的最适合和验证的模型。在这次审查中,我们讨论了脱髓鞘的病理生理学，并总结了当前髓鞘再生剂的临床试验情况。我们提出了髓鞘再生剂研究中的一些挑战，并讨论了当前髓鞘再生和修复的潜在生物标志物。强调既定和新兴的视觉结果措施。
