Indelicato Elisabetta, Delatycki Martin B, Farmer Jennifer, França Marcondes C, Perlman Susan, Rai Myriam, Boesch Sylvia
Center for Rare Movement Disorders Innsbruck, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Nat Rev Neurol. 2025 Apr;21(4):204-215. doi: 10.1038/s41582-025-01065-y. Epub 2025 Mar 3.
Friedreich ataxia (FRDA) is a rare multisystem, life-limiting disease and is the most common early-onset inherited ataxia in populations of European, Arab and Indian descent. In recent years, substantial progress has been made in dissecting the pathogenesis and natural history of FRDA, and several clinical trials have been initiated. A particularly notable recent achievement was the approval of the nuclear factor erythroid 2-related factor 2 activator omaveloxolone as the first disease-specific therapy for FRDA. In light of these developments, we review milestones in FRDA translational and clinical research over the past 10 years, as well as the various therapeutic strategies currently in the pipeline. We also consider the lessons that have been learned from failed trials and other setbacks. We conclude by presenting a global roadmap for future research, as outlined by the recently established Friedreich's Ataxia Global Clinical Consortium, which covers North and South America, Europe, India, Australia and New Zealand.
弗里德赖希共济失调(FRDA)是一种罕见的多系统、危及生命的疾病,是欧洲、阿拉伯和印度裔人群中最常见的早发性遗传性共济失调。近年来,在剖析FRDA的发病机制和自然史方面取得了重大进展,并启动了多项临床试验。最近一项特别显著的成就是核因子红细胞2相关因子2激活剂奥马伐索隆获批,成为首个针对FRDA的疾病特异性疗法。鉴于这些进展,我们回顾了过去10年FRDA转化研究和临床研究的里程碑,以及目前正在进行的各种治疗策略。我们还考虑了从失败的试验和其他挫折中吸取的教训。最后,我们提出了一份全球未来研究路线图,这是由最近成立的弗里德赖希共济失调全球临床联盟制定的,该联盟覆盖北美和南美、欧洲、印度、澳大利亚和新西兰。