Reviews

Volume XLIV n. 1 - March 2025

Deciphering Facioscapulohumeral Dystrophy in the clinical trials era: where are we now?

Authors

Francesca Torri , Beatrice Ciurli , Mariaconcetta Rende , Arianna Votta , Emanuele Mocciaro , Frida Karakashi , Matteo Leoncini , Elisabetta Ferraro , Massimiliano Filosto , Davide Gabellini , Gabriele Siciliano , Giulia Ricci

Key words: Facioscapulohumeral muscular dystrophy (FSHD), DUX4, Clinical variability, Therapeutic strategies, Clinical trials
DOI: 10.36185/2532-1900-1047
Publication Date: 2025-02-26

Abstract

Objectives. Facioscapulohumeral muscular dystrophy (FSHD) is a common genetic disorder characterized by progressive muscle weakness, especially in the face, shoulders, and upper limbs. Despite extensive research, the underlying pathogenesis and clinical variability remain incompletely understood. This review aims to summarize recent advances in FSHD research, focusing on genetic and epigenetic factors and the potential for precision medicine.
Methods. A comprehensive review of recent literature was conducted, examining molecular mechanisms such as mutations in the D4Z4 region, DUX4 expression, RNA interference (RNAi) and antisense oligonucleotides (AOs). Clinical variability was analyzed to assess different disease phenotypes. Clinical trials investigating potential treatments, especially those targeting DUX4, were also reviewed.
Results. FSHD shows significant clinical variability, with different progression rates across phenotypes. The 4qA allele is linked to more typical forms of the disease, but epigenetic factors, including DNA methylation and miRNA expression, also influence disease severity. Despite progress, the exact molecular mechanisms driving disease expression remain unclear. Clinical trials, such as Losmapimod, show promise in slowing muscle degeneration, though results remain inconsistent.
Conclusions. FSHD presents significant challenges for therapy development due to its genetic complexity and clinical variability. Ongoing research is needed to clarify pathogenesis and identify reliable biomarkers. Future therapeutic strategies should focus on precision medicine, integrating genetic, clinical, and imaging data to optimize patient stratification and treatment efficacy.

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Authors

Francesca Torri - Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa, Italy

Beatrice Ciurli - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Mariaconcetta Rende - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Arianna Votta - Department of Biology, Unit of cell and Developmental Biology, University of Pisa, Pisa, Italy

Emanuele Mocciaro - Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy

Frida Karakashi - Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy

Matteo Leoncini - UO Plastic Surgery, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy

Elisabetta Ferraro - Department of Biology, Unit of cell and Developmental Biology, University of Pisa, Pisa, Italy

Massimiliano Filosto - Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

Davide Gabellini - Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy

Gabriele Siciliano - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Giulia Ricci - Department of Clinical and Experimental Medicine, University of Pisa

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright

Copyright (c) 2024 Acta Myologica

How to Cite
Torri, F. ., Ciurli, B. ., Rende , M., Votta, A., Mocciaro, E., Karakashi, F., Leoncini, M. ., Ferraro, E., Filosto, M., Gabellini, D. ., Siciliano, G., & Ricci, G. (2025). Deciphering Facioscapulohumeral Dystrophy in the clinical trials era: where are we now?. Acta Myologica, 44(1). https://doi.org/10.36185/2532-1900-1047
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