Systemic delivery of a DUX4-targeting antisense oligonucleotide to treat facioscapulohumeral muscular dystrophy
Linde F. Bouwman, Bianca den Hamer, Anita van den Heuvel, Marnix Franken, Michaela Jackson, Chrissa A. Dwyer, Stephen J. Tapscott, Frank Rigo, Silvère M. van der Maarel, Jessica C. de Greef
Abstract
target gene expression in skeletal muscles. In addition, the DUX4 ASO alleviated the severity of skeletal muscle pathology and partially prevented the dysregulation of inflammatory and extracellular matrix genes. DUX4 ASO-treated ACTA1-MCM;FLExDUX4 mice performed better on a treadmill; however, the hanging grid and four-limb grip strength tests were not improved compared to control ASO-treated ACTA1-MCM;FLExDUX4 mice. This study shows that systemic delivery of ASOs targeting DUX4 is a promising therapeutic strategy for FSHD and strategies that further improve the ASO efficacy in skeletal muscle are warranted.