Duchenne cardiomyopathy refers to heart-associated clinical manifestations seen in Duchenne muscular dystrophy (DMD). DMD is caused by mutations in the dystrophin gene. Cardiac involvement occurs in all DMD patients, and up to 40% of patients die from heart failure or sudden cardiac death. Currently, there is no disease-specific therapy for Duchenne cardiomyopathy. We have recently ameliorated dystrophic skeletal muscle disease and improved muscle force in the mdx mouse model of DMD using CRISPR/Cas9, a revolutionary genome editing technology. Specifically, we removed the mutated region in the genome with a molecular knife called Cas9. The healthy parts of the dystrophin gene are sutured together by cellular DNA repair machinery. This targeted molecular surgery provides a once-for-all solution to restore dystrophin expression for good. Based on this success, we propose to test this "permanent exon skipping" therapy to the treatment of Duchenne cardiomyopathy in an authentic mouse model. Our study will open the door to the eventual application of CRISPR/Cas9 therapy in human patients in the future. |
