Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial

作者：Kimberly Y. Lin, Anna Bucha, K. McSweeney, Kristin Wade, Antoneta Karaj, Jaclyn Tamaroff, Shannon O’Malley, Nicole M Chung, Nicolette Cilenti, Julianne Wanner, Gabriel Komla Adzika, Clementina Mesaros, Ian A. Blair, Teerapat Rojsajjakul, Suraj Serai, Jennifer Farmer, Kyle Bryant, Yingying Lu, Michael O. Harhay, David R. Weber, Stephen M. Paridon, Erin L Seifert, Mary Putt, Payman Zamani, Joseph A. Baur, David A Lynch, Shana E. McCormack · 发表于：The Lancet Neurology · 年份：2026 · DOI：10.1016/s1474-4422(26)00082-7 · 被引用次数：2 · 研究领域：Genetic Neurodegenerative Diseases、Amyotrophic Lateral Sclerosis Research、Hereditary Neurological Disorders

Background Friedreich's ataxia is a rare, chronic, progressive, neurodegenerative condition affecting multiple organ systems, including neurological, musculoskeletal, cardiac, and endocrine systems, and is marked by low cardiopulmonary fitness. We tested the effect of exercise and NAD + precursor supplementation with nicotinamide riboside, which have each shown benefits in animal and early clinical studies, on cardiopulmonary fitness in individuals with Friedreich's ataxia. Methods This 12-week, outpatient, phase 2, single-site (Children's Hospital of Philadelphia, Philadelphia, PA, USA), randomised, 2 × 2 factorial clinical trial recruited individuals aged 10–40 years with an ejection fraction of 45% or greater who were able to exercise. A computer-generated randomisation sequence was developed by the trial statistician. Random allocation was age-stratified (<18 years vs ≥18 years) to one of four groups: placebo and no exercise with attention control (weekly phone calls; henceforth placebo only), nicotinamide riboside and no exercise with attention control (henceforth nicotinamide riboside only), placebo and exercise (exercise only), and nicotinamide riboside and exercise (combination therapy). Individualised exercise plans were developed by the exercise physiologist (three aerobic and two resistance training sessions weekly), performed at the individual's home, and overseen remotely (telephone check-ins by the physiologist). Weight-based dosing of nicotinamide riboside or p...