Advances in the molecular understanding of facioscapulohumeral muscular dystrophy (FSHD) have revealed that FSHD results from epigenetic de-repression of the DUX4 gene in skeletal muscle, which encodes a transcription factor that is active in early embryonic development but is normally silenced in almost all somatic tissues. These advances also led to the identification of targets for disease-altering therapies for FSHD, as well as an improved understanding of the molecular mechanism of the disease and factors that influence its progression. Together, these developments led the FSHD research community to shift its focus towards the development of disease-modifying treatments for FSHD. This Review presents advances in the molecular and clinical understanding of FSHD, discusses the potential targeted therapies that are currently being explored, some of which are already in clinical trials, and describes progress in the development of FSHD-specific outcome measures and assessment tools for use in future clinical trials.
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