Accession Number:



Treating Duchenne Cardiomyopathy in the Mouse Model by Gene Repair

Descriptive Note:

Technical Report,01 Aug 2016,31 Jul 2017

Corporate Author:

University of Missouri System Columbia United States

Report Date:


Pagination or Media Count:



The goal of this project is to test adeno-associated virus AAV CRISPR clustered regularly interspaced palindromic repeat gene editing therapy for Duchenne cardiomyopathy in the mdx model. In this funding period, we performed AAV CRISPR therapy in young adult mdx mice. We observed widespread dystrophin restoration in the heart on immunostaining. However, western blot showed only 5 dystrophin restoration. Nevertheless, we detected persistent gene editing till mice reached 18 months of age. Cardiac histology was not improved. Neither was the blood pumping function. Limited improvement was noticed in some ECG parameters. Surprisingly, mice treated at the young age showed a statistically significant body weight reduction despite the absence of off-target editing in the predicted locations. To determine therapeutic relevance of low-level dystrophin expression, we also examined mdx3cv mice. These mice expressed 3.3 dystrophin in the heart on western blot. They showed characteristic cardiac pathology and abnormal ECG although their hemodynamic performance was better than dystrophin-null mice. In summary, our results suggest that the low-level dystrophin restoration obtained from the current AAV CRISPR technology is insufficient to substantially improve Duchenne cardiomyopathy. Unexpected weight loss cautions on potential side effects of this therapy. In next funding period, we will explore novel strategies to improve gene-editing efficiency. We will also examine whether weight loss is a real safety concern.

Subject Categories:

  • Medicine and Medical Research
  • Anatomy and Physiology
  • Genetic Engineering and Molecular Biology

Distribution Statement: