Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.
Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
CNS Drugs. 2024 Oct;38(10):791-805. doi: 10.1007/s40263-024-01113-z. Epub 2024 Aug 8.
The life shortening nature of Friedreich Ataxia (FRDA) demands the search for therapies that can delay, stop or reverse its relentless trajectory. This review provides a contemporary position of drug and gene therapies for FRDA currently in phase 1 clinical trials and beyond. Despite significant scientific advances in the specificity of both compounds and targets developed and investigated, challenges remain for the advancement of treatments in a limited recruitment population. Currently therapies focus on reducing oxidative stress and improving mitochondrial function, modulating frataxin controlled metabolic pathways and gene replacement and editing. Approval of omaveloxolone, the first treatment for individuals with FRDA aged 16 years and over, has created much excitement for both those living with FRDA and those that care for them. The process of approval of omaveloxolone by the US Food and Drug Administration highlighted the importance of sensitive outcome measures and the significant role of data from natural history studies.
弗里德赖希共济失调(FRDA)的生命缩短性质要求寻找能够延缓、阻止或逆转其无情轨迹的治疗方法。 本综述提供了 FRDA 目前处于 1 期临床试验及以后的药物和基因治疗的最新进展。 尽管在开发和研究的化合物和靶点的特异性方面取得了重大科学进展,但在有限的招募人群中推进治疗仍存在挑战。 目前的治疗方法侧重于减轻氧化应激和改善线粒体功能,调节受 frataxin 控制的代谢途径以及基因替换和编辑。 批准用于年龄在 16 岁及以上 FRDA 患者的 omaveloxolone 是第一个治疗方法,这让 FRDA 患者及其照顾者都感到非常兴奋。美国食品和药物管理局批准 omaveloxolone 的过程强调了敏感结果测量的重要性以及自然史研究数据的重要作用。