Recent progress in the molecular understanding and treatments of facioscapulohumeral muscular dystrophy.

Objective: 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.

Results: 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.

Conclusions: 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.