Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 0AH, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
Curr Opin Pharmacol. 2022 Oct;66:102269. doi: 10.1016/j.coph.2022.102269. Epub 2022 Aug 1.
Remyelination is the regenerative process by which lost myelin sheaths are restored to demyelinated axons. It is a key target in the treatment of chronic demyelinating disorders such as multiple sclerosis (MS), in which inflammation results in destruction of myelin. In the central nervous system (CNS), remyelination typically requires the differentiation of oligodendrocyte progenitor cells (OPCs) into the myelinating oligodendrocytes (OL). Following successes in preclinical studies, several putative pro-regenerative therapies aimed at enhancing remyelination are under clinical investigation. However, there is a translational barrier in identifying successful outcomes: preclinical measures of remyelination do not translate well to clinical studies, and the paraclinical measures currently deployed in trials are challenging to apply to small rodent models of remyelination. Here, we describe the current approaches to identifying remyelination both in preclinical and clinical settings and highlight exciting translational candidates, which may help to bridge the current impasse.
髓鞘修复是指失去的髓鞘鞘被重新修复到脱髓鞘轴突的再生过程。它是治疗多发性硬化症（MS）等慢性脱髓鞘疾病的关键靶点，其中炎症导致髓鞘破坏。在中枢神经系统（CNS）中，髓鞘修复通常需要少突胶质前体细胞（OPC）分化为髓鞘形成的少突胶质细胞（OL）。在临床前研究取得成功后，几种旨在增强髓鞘修复的潜在再生治疗方法正在进行临床研究。然而，在确定成功结果方面存在转化障碍：临床前的髓鞘修复测量方法不能很好地转化为临床研究，目前在试验中使用的临床前测量方法难以应用于小型啮齿动物的髓鞘修复模型。在这里，我们描述了在临床前和临床环境中识别髓鞘修复的当前方法，并强调了令人兴奋的转化候选者，这可能有助于弥合当前的僵局。
