Zejing Wang, associate in clinical research at the Fred Hutchinson Cancer Research Center in Seattle, was awarded an MDA research grant totaling $300,000 over a period of three years to develop gene therapy for Duchenne muscular dystrophy (DMD) — with a focus on treating the heart — in a canine (dog) model of the disease.
DMD is caused by a mutation in the dystrophin gene. Gene therapy in DMD has focused on delivering the gene via a viral vector, or carrier, derived from adeno-associated virus (AAV).
“Despite encouraging results using AAV-mediated delivery of dystrophin into skeletal muscles,” says Wang, “few attempts have been made to genetically treat cardiomyopathy.” Cardiomyopathy, or disease of the heart muscle, remains a major cause of death in DMD, with few treatments available.
Mutations in dystrophin also occur naturally in some dog breeds, making them an important model for studying treatment of the disease.
“Our project will develop AAV-mediated gene therapy for treating cardiomyopathy in a preclinical DMD dog model that can then be applied to treat human DMD patients suffering from cardiac failure. The preclinical DMD dog model represents the most relevant animal model that faithfully mimics human DMD, reproducing many of its features not seen in the mouse model, including cardiomyopathy.”
Wang’s work will focus on improving the ability of the AAV vector to enter heart muscle cells and carry on long-term dystrophin production there.
“Developing strategies for efficient gene delivery and sustained transgene expression in heart muscle will increase the likelihood of achieving the goal of effective gene therapy and the ultimate reduction of mortality in DMD patients,” he says.
Funding for this MDA grant began August 1, 2013.