Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
Multiple Sclerosis Society, London, UK.
J Neurol Neurosurg Psychiatry. 2021 Mar;92(3):295-302. doi: 10.1136/jnnp-2020-324286. Epub 2020 Nov 12.
To establish a rigorous, expert-led, evidence-based approach to the evaluation of licensed drugs for repurposing and testing in clinical trials of people with progressive multiple sclerosis (MS).
We long-listed licensed drugs with evidence of human safety, blood-brain barrier penetrance and demonstrable efficacy in at least one animal model, or mechanistic target, agreed by a panel of experts and people with MS to be relevant to the pathogenesis of progression. We systematically reviewed the preclinical and clinical literature for each compound, condensed this into a database of summary documents and short-listed drugs by scoring each one of them. Drugs were evaluated for immediate use in a clinical trial, and our selection was scrutinised by a final independent expert review.
From a short list of 55 treatments, we recommended four treatments for immediate testing in progressive MS: R-α-lipoic acid, metformin, the combination treatment of R-α-lipoic acid and metformin, and niacin. We also prioritised clemastine, lamotrigine, oxcarbazepine, nimodipine and flunarizine.
We report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.
建立一种严格、以专家为主导、基于证据的方法，用于评估有前景的药物在临床试验中的重新定位和测试，以治疗进展性多发性硬化症（MS）患者。
我们将具有人类安全性证据、血脑屏障穿透性证据和至少在一种动物模型或机制靶点中表现出疗效的已上市药物列入长名单，这些靶点由一组专家和 MS 患者共同确定与进展性疾病的发病机制相关。我们系统地回顾了每个化合物的临床前和临床文献，将其浓缩为一个摘要文档数据库，并对每个化合物进行评分，以确定短名单药物。我们评估了这些药物在临床试验中的直接应用，并通过最终的独立专家审查对我们的选择进行了仔细审查。
从 55 种治疗方法的短名单中，我们推荐了四种药物立即用于治疗进展性 MS：R-α-硫辛酸、二甲双胍、R-α-硫辛酸和二甲双胍的联合治疗以及烟酸。我们还优先考虑了氯苯那敏、拉莫三嗪、奥卡西平、尼莫地平、氟桂利嗪。
我们报告了一种标准化的方法，用于鉴定有前景的药物，以重新用于治疗进展性 MS。
