Data from: Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis

Objective: To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis. Design: Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action. Results: We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for clinical evaluation. Conclusions: We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

研究目标：开发并实施一套循证框架，用于从已获批上市药物中筛选候选口服神经保护药物，以在继发性进展型多发性硬化（secondary progressive multiple sclerosis）中开展临床试验验证。
研究设计：首先针对口服潜在神经保护治疗药物用于多发性硬化（multiple sclerosis, MS）及其他4种具有共同病理特征的神经退行性疾病的临床研究开展系统综述；随后针对上述干预措施开展体内实验数据的系统综述与荟萃分析（meta-analyses）。我们将汇总分析后的研究数据提交至国际多学科委员会，该委员会按照预先设定的评估标准依次审查每一种药物，包括考量其作用机制。
研究结果：本研究初步筛选出52种候选干预措施。在审阅全部临床及临床前研究证据后，我们确定依布司他（ibudilast）、利鲁唑（riluzole）、阿米洛利（amiloride）、吡非尼酮（pirfenidone）、氟西汀（fluoxetine）、奥卡西平（oxcarbazepine）以及多不饱和脂肪酸类（包含亚油酸（Linoleic Acid）、硫辛酸（Lipoic acid）、Omega-3脂肪酸（Omega-3 fatty acid）、Max EPA油）作为可进入临床评估的首选候选药物。
研究结论：本研究证实了一套标准化、系统化的药物重定位与挽救试验候选药物鉴定流程，该流程可广泛应用于各类神经退行性疾病的相关研究中。