Augustinus Roy, Voet Nicole, de Greef Jessica C, Voermans Nicol C
Department of Human Genetics, Leiden University Medical Center, Leiden.
Department of Rehabilitation, Donders Institute for Brain, Cognition and Behaviour, Amalia Children's Hospital, Radboud University Medical Centre, Nijmegen.
Curr Opin Neurol. 2025 Oct 1;38(5):504-512. doi: 10.1097/WCO.0000000000001382. Epub 2025 Jun 5.
Facioscapulohumeral muscular dystrophy (FSHD) is a progressive inherited myopathy, for which there is currently no cure available. This review focuses on the recent progress in the molecular understanding and treatments of FSHD.
Recent studies on the molecular understanding of FSHD highlight its multifaceted complexity and suggest new targets for therapeutic intervention. Preclinical models, such as the 3D skeletal muscle, provide an easier way to study molecular pathways and serve as a platform for drug screenings. New insights on training and the new international guideline contribute to optimal symptomatic treatment. In parallel, research is advancing with generic and targeted molecular therapies aiming to inhibit DUX4 activity or its downstream effects.
FSHD is caused by abnormal expression of the DUX4 gene. Our understanding of the molecular mechanisms underlying DUX4 and DUX4 target gene expression remains incomplete. However, advancements continue to clarify the roles of key proteins and genes, which might be of interest for future therapeutic therapies. Current therapies, treatments, and clinical trials for FSHD focus on molecular approaches, gene therapy, and symptom management. These developments indicate a growing focus on precision treatments and functional assessments, paving the way for improved FSHD management.
面肩肱型肌营养不良症（FSHD）是一种进行性遗传性肌病，目前尚无治愈方法。本综述聚焦于FSHD在分子认识和治疗方面的最新进展。
近期关于FSHD分子认识的研究突出了其多方面的复杂性，并提出了治疗干预的新靶点。临床前模型，如3D骨骼肌，为研究分子途径提供了更便捷的方式，并作为药物筛选的平台。关于训练的新见解和新的国际指南有助于实现最佳的对症治疗。与此同时，针对抑制DUX4活性或其下游效应的通用和靶向分子疗法的研究也在推进。
FSHD由DUX4基因的异常表达引起。我们对DUX4及其靶基因表达背后分子机制的理解仍不完整。然而，研究进展不断阐明关键蛋白质和基因的作用，这可能对未来的治疗有意义。目前FSHD的治疗方法、治疗手段和临床试验聚焦于分子方法、基因治疗和症状管理。这些进展表明对精准治疗和功能评估的关注度不断提高，为改善FSHD的管理铺平了道路。
