Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis
Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis
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DOI：
10.1136/jnnp-2020-324286
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发表时间：
2021-03-01
影响因子：
11
通讯作者：
Coles，Alasdair
中科院分区：
文献类型：
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作者：
Cunniffe，Nick;Coles，Alasdair
目的建立一种严格的、专家主导的、以证据为基础的方法来评估已获批药物的再利用和在进行性多发性硬化症（MS）患者的临床试验中进行测试。方法：我们长期上市的许可药物具有人体安全性，血脑屏障外显性和至少一种动物模型或机制靶点的可证明的有效性，经专家小组和MS患者同意与进展的发病机制相关。我们系统地回顾了每种化合物的临床前和临床文献，并将其浓缩为摘要文献和候选药物数据库，并对每种化合物进行评分。在临床试验中立即使用药物进行评估，我们的选择由最终独立专家审查。结果从55种治疗方法中，我们推荐了4种治疗方法用于进展性MS的即时检测：R-α-硫辛酸、二甲双胍、R-α-硫辛酸与二甲双胍联合治疗、烟酸。我们还优先考虑了克莱马斯汀、拉莫三嗪、奥卡西平、尼莫地平和氟桂利嗪。结论：我们报告了一种标准化的方法来确定用于治疗进展性MS的候选药物。
ObjectiveTo 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).MethodsWe 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.ResultsFrom 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.ConclusionsWe report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.