Nonviral Targeted Gene Delivery for Full-Length Dystrophin Expression in DMD Skeletal and Cardiac Muscle
Abstract
We have developed a novel, non-viral gene therapy method for treating Duchenne muscular dystrophy (DMD) that is superior to adeno-associated viral delivery currently being used to deliver micro-dystrophin. Our delivery platform targets dystrophin expression to skeletal and heart muscle. Furthermore, it can deliver full-length dystrophin, rather than the much smaller and less functional micro-dystrophins. Also, our platform can avoid the immune responses that are common in AAV gene delivery. Finally, we have evidence that multiple doses can be safely given to increase and maintain the level of dystrophin expression, likely over many months or years. Finally, our results suggest that even small amounts of full-length dystrophin significantly reduce muscle damage in a DMD animal model. Our new non-viral gene therapy method is applicable to all DMD patients. We anticipate that treatment of young DMD boys will be the most beneficial, but it is possible that boys and men with more advanced muscle degeneration and cardiomyopathy might also be effectively treated. Whether studies in the mouse model of DMD will translate to human patients is always a question. However, a recent publication revealed that DMD patients with even very small amounts of full-length dystrophin remain ambulatory for many years and their lifespan is much longer. Thus, our preliminary studies in mice are consistent with these findings in humans. The pre-clinical studies proposed in this application will allow us to refine the platform to achieve optimal function and minimize the possibility that it may elicit an immune reaction. This information will set the stage for clinical development studies in approximately 2 years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210659
Entities
People
- Stanley Froehner
Organizations
- United States Army
- University of Washington