Pig models for translational Duchenne muscular dystrophy research.

Abstract

Duchenne muscular dystrophy (DMD) is caused by mutations in the X-linked DMD gene, resulting in the absence of dystrophin, progressive muscle degeneration, and heart failure. Genetically tailored pig models resembling human DMD mutations recapitulate the biochemical, clinical, and pathological hallmarks of DMD with an accelerated disease progression compared to human patients. DMD pigs have been used to evaluate therapeutic concepts such as gene editing to reframe a disrupted DMD reading frame or the delivery of artificial chromosome vectors carrying the complete DMD gene. Moreover, DMD pigs have been instrumental in validating new diagnostic modalities such as multispectral optoacoustic tomography (MSOT) for non-invasive monitoring of disease progression. DMD pigs may thus help to bridge the gap between proof-of-concept studies in cellular or rodent models and clinical studies in patients.