Moretti, A. et al. Nat. Med. (2020) 10.1038/s41591-019-0738-2

Duchenne muscular dystrophy (DMD) is an inherited and eventually fatal myopathy that affects about 1 in 5000 newborn boys. The mutation responsible, a frameshift mutation affecting the gene that produces the dystrophin protein in muscles, maybe however be amenable to gene therapy. Trials in patients have been limited, but CRISPR/Cas9-based therapies delivered via adeno-associated virus vectors have shown promise in mouse and canine models. New work from researchers in Munich adds another large animal: the pig.

The team generated a pig model of DMD; these animals do not express dystrophin and display muscle weakness, signs of cardiac myopathy, and experience premature death. A CRISPR/Cas9-based therapy, delivered intravenously, was able to restore dystrophin expression in muscles such as the diaphragm and heart and prolong lifespans in the pig model.