Carroll Emily, Scaber Jakub, Huber Kilian V M, Brennan Paul E, Thompson Alexander G, Turner Martin R, Talbot Kevin
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.
Expert Opin Drug Discov. 2025 Apr;20(4):447-464. doi: 10.1080/17460441.2025.2474661. Epub 2025 Mar 7.
Identifying treatments that can alter the natural history of amyotrophic lateral sclerosis (ALS) is challenging. For years, drug discovery in ALS has relied upon traditional approaches with limited success. Drug repurposing, where clinically approved drugs are reevaluated for other indications, offers an alternative strategy that overcomes some of the challenges associated with de novo drug discovery.
In this review, the authors discuss the challenge of drug discovery in ALS and examine the potential of drug repurposing for the identification of new effective treatments. The authors consider a range of approaches, from screening in experimental models to computational approaches, and outline some general principles for preclinical and clinical research to help bridge the translational gap. Literature was reviewed from original publications, press releases and clinical trials.
Despite remaining challenges, drug repurposing offers the opportunity to improve therapeutic options for ALS patients. Nevertheless, stringent preclinical research will be necessary to identify the most promising compounds together with innovative experimental medicine studies to bridge the translational gap. The authors further highlight the importance of combining expertise across academia, industry and wider stakeholders, which will be key in the successful delivery of repurposed therapies to the clinic.
确定能够改变肌萎缩侧索硬化症（ALS）自然病程的治疗方法具有挑战性。多年来，ALS的药物研发一直依赖传统方法，但成效有限。药物重新定位，即对临床已批准药物进行其他适应症的重新评估，提供了一种替代策略，可克服一些与从头研发新药相关的挑战。
在本综述中，作者讨论了ALS药物研发的挑战，并研究了药物重新定位在确定新的有效治疗方法方面的潜力。作者考虑了一系列方法，从实验模型筛选到计算方法，并概述了临床前和临床研究的一些一般原则，以帮助弥合转化差距。对原始出版物、新闻稿和临床试验的文献进行了综述。
尽管仍存在挑战，但药物重新定位为改善ALS患者的治疗选择提供了机会。然而，需要严格的临床前研究来确定最有前景的化合物，同时需要创新的实验医学研究来弥合转化差距。作者进一步强调了整合学术界、产业界和更广泛利益相关者专业知识的重要性，这对于成功将重新定位的疗法推向临床至关重要。
