(From left) Jonathan Lindner, MD, and Brent French, PhD
Jonathan Lindner, MD, the Francis Myers Ball Professor of Medicine and vice-chief for research in the Division of Cardiovascular Medicine, and Brent French, PhD, a professor of biomedical engineering, radiology and cardiovascular medicine, were awarded a $2.9 million NIH grant, titled “Ultrasound Cavitation for Facilitated Cardiac Transduction of AAV.”
Gene therapy to the heart is a major focus for treating inherited diseases of the heart muscle (cardiomyopathy) such as hypertrophic cardiomyopathy, genetic dilated cardiomyopathies, forms of infiltrative myopathies and primary arrhythmic disorders. Clinically meaningful gene therapy relies on delivery of genetic material to myocytes that is both efficient and safe. Bioengineered adeno-associated viruses (AAV), which are members of the parvovirus family, are increasingly used as a vector to achieve successful gene therapy in patients. A major limiting factor has been the large AAV dose needed to achieve beneficial effects in the heart, leading to serious adverse events and discontinuation of several major clinical trials.
Drs. Lindner and French will use this award to lay the foundation for using ultrasound mediated vibration (cavitation) of microbubble contrast agents, a technology pioneered at the University of Virginia, to focally enhance AAV-mediated gene therapy in the heart. The work will include optimization of acoustic conditions, mechanism of action, proof of efficacy and safety in non-human primate models and proof-of-principle evaluation of therapeutic effect to reverse hypertrophic cardiomyopathy.
Completion of the studies will provide the groundwork for translating these technologies to human trials where innovative use of AAV therapy in the heart has been limited by dose-related adverse effects.
Filed Under: Research