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Neurotherapeutics
Erschienen in: Neurotherapeutics 4/2018

01.10.2018 | Review

Facioscapulohumeral Muscular Dystrophy: Update on Pathogenesis and Future Treatments

verfasst von: Johanna Hamel, Rabi Tawil

Erschienen in: Neurotherapeutics | Ausgabe 4/2018

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Abstract

A reliable model of a disease pathomechanism is the first step to develop targeted treatment. In facioscapulohumeral muscular dystrophy (FSHD), the third most common muscular dystrophy, recent advances in understanding the complex genetics and epigenetics have led to the identification of a disease mechanism, moving the field towards targeted therapy development. FSHD is caused by expression of DUX4, a retrogene located on the D4Z4 macrosatellite repeat array on chromosome 4q35, a gene expressed in the germline but typically repressed in somatic tissue. DUX4 derepression results from opening of the chromatin structure either by contraction of the number of repeats (FSHD1) or by chromatin hypomethylation of the D4Z4 repeats resulting from mutations in SMCHD1, a gene involved in chromatin methylation (FSHD2). The resulting expression of DUX4, a transcriptional regulator, and its target genes is toxic to skeletal muscle. Efforts for targeted treatment currently focus on disrupting DUX4 expression or blocking 1 or more of several downstream effects of DUX4. This review article focuses on the underlying FSHD genetics, current understanding of the pathomechanism, and potential treatment strategies in FSHD. In addition, recent advances in the development of new clinical outcome measures as well as biomarkers, critical for the success of future clinical trials, are reviewed.
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Metadaten
Titel
Facioscapulohumeral Muscular Dystrophy: Update on Pathogenesis and Future Treatments
verfasst von
Johanna Hamel
Rabi Tawil
Publikationsdatum
01.10.2018
Verlag
Springer International Publishing
Erschienen in
Neurotherapeutics / Ausgabe 4/2018
Print ISSN: 1933-7213
Elektronische ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-018-00675-3

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