Sean C. Forbes1, Larry T. Bish2,
Meg M. Sleeper3, Wil Mai4, H. Sweeney2,
Glenn A. Walter5
1Department of Physical
Therapy, University of Florida, Gainesville, FL, United States; 2Department
of Physiology, University of Pennsylvania, Philadelphia, PA; 3Department
of Clinical Studies, University of Pennsylvania, Philadelphia, PA; 4School
of Veterinary Medicine, University of Florida, Philadelphia, PA; 5Department
of Physiology & Functional Genomics, University of Florida, Gainesville,
FL
Cardiac dysfunction is prevalent in Duchennes muscular dystrophy (DMD), with heart failure a common cause of death. Unfortunately, there is presently no cure or effective treatment for DMD. This study implements a novel approach of exon skipping by using viral mediated delivery of a modified U7 snRNA carrying antisense sequence to correct the disrupted reading frame in Golden Retriever muscular dystrophy (GRMD) dogs. The results indicate increased dystrophin expression and improved regional left ventricular strain values. Thus, AAV-mediated delivery of a U7 exon skipping construct shows promise as a cardiac therapeutic intervention for DMD.
Keywords