More or less promising new therapeutic approaches in FSH

Facioscapulohumeral myopathy (FSH) results in progressive damage to the muscles of the face, the fixators of the scapula, the muscles of the trunk and the levator muscles of the feet. There are two types, FSH1 (95% of cases) and FSH2 (5% of cases). In both types, the DUX4 gene is abnormally expressed. It encodes the DUX4 transcription factor, which, by cascade activation of other genes, is involved in the destruction of muscle fibers. 

In two articles published in October and December 2020, the team of J. Dumonceaux (University College London in London) published the results of approaches seeking to inhibit the DUX4 gene or to trap the DUX4 protein. In the first case, it used a “gene editing” approach with TALENs or with the CRISPR / Cas 9 system targeting the polyadenylation signal of the DUX4 gene. While this approach did eliminate the polyadenylation signal from the gene, it did not, however, prevent the production of DUX4 messenger RNA. 

In the other article, J. Dumonceaux’s team reports the proof of principle of the feasibility of a strategy aimed at deceiving the DUX4 transcription factor, from the work presented at the Myology Congress organized by the AFM-Téléthon in 2019. Transfection of “decoys” into myotubes affected with FSH or FSH model mice enabled to trap the DUX4 protein and reduce the expression of genes activated by DUX4.


A Deoxyribonucleic Acid Decoy Trapping DUX4 for the Treatment of Facioscapulohumeral Muscular Dystrophy. V Mariot, RJoubert, ACMarsollier et al. Mol Ther Nucleic Acids. 2020 (Oct).22:1191-1199.


Gene Editing Targeting the DUX4 Polyadenylation Signal: A Therapy for FSHD? R Joubert, V Mariot, M Charpentier et al. J Pers Med. 2020 (Dec).11(1):E7.