Systemic injection of an optimized antisense oligonucleotide into an FSH mouse model appears to be effective

Facioscapulohumeral dystrophy (FSH) is one of the most common myopathies. There are two forms, FSH1 and FSH2. In both cases, the DUX4 gene is abnormally expressed in the muscles. 

In an effort to inhibit DUX4, Canadian researchers have optimized antisense oligonucleotides by coupling them to a peptide that favors their penetration into muscle cells. This optimized antisense oligonucleotide, Vivo-PMO PACS4, administered systemically over a month to a transgenic mouse model whose skeletal muscle expression of DUX4 was induced by tamoxifen.

The results published in May 2021 showed in these mice: 

  • a 50% decrease in the expression of DUX4 and genes activated by DUX4, 
  • a 12% improvement in muscle atrophy and 52% improvement in muscle strength
  • a 17% reduction in muscle fibrosis and a 12% reduction in fatigue,
  • an improved locomotor activity.

An American team, which has developed its own antisense oligonucleotide, confirms these results. Their product, injected subcutaneously twice a week for 10 weeks into model mice, also reduced the expression of DUX4 and its targets and reduced muscle fatigue in treated mice.


Systemic antisense therapeutics inhibiting DUX4 expression ameliorates FSHD-like pathology in an FSHD mouse model. Lu-Nguyen N, Malerba A, Herath S, Dickson G, Popplewell L. Hum Mol Genet. 2021 (Mai).


Systemic delivery of a DUX4-targeting antisense oligonucleotide to treat facioscapulohumeral muscular dystrophy. Linde F Bouwman, Bianca den Hamer, Anita van den Heuvel  et al. Mol Ther Nucleic Acids . 2021 (Dec)