Pig models for translational Duchenne muscular dystrophy research.

Pigs can be genetically engineered to resemble human monogenic diseases. Genetically tailored pig models may bridge the gap between proof-of-concept studies in cellular or rodent models and clinical trials. DMD pigs show the characteristic biochemical, clinical, and pathological features of DMD, with an accelerated development of the disease. DMD pigs provide new insights into the hierarchy of physiological abnormalities of dystrophic muscle. DMD pigs are a promising model for testing targeted therapies, such as exon skipping and gene editing, as well as for validating and optimizing novel diagnostic procedures such as MSOT. 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. [ABSTRACT FROM AUTHOR]