New Avenues to Treat Heart Failure Using an Engineered Enzyme and Human Pluripotent Stem Cells
Principal Investigator: Timothy Kamp, professor of medicine/cardiovascular medicine
Matthew Brown, assistant professor of surgery
Aaron LeBeau, associate professor of radiology
Philip Romero, assistant professor of biochemistry
Timothy Hacker, scientist III at the Cardiovascular Research Center
Peter Heinzelman, scientist II in biochemistry
Following a myocardial function (MI), the lack of regenerative potential in the adult human heart results in muscle being replaced by scar tissue. For many post-MI patients, progressive adverse cardiac remodeling occurs leading to heart failure (HF).
Despite multiple drugs to treat HF, the overall mortality five years after diagnosis remains ~50%. Neurohormonal signaling is central to the progression of heart failure, and Angiotensin-Converting Enzyme 2 (ACE2) is a promising biotherapeutic protein that can uniquely blunt the pro-inflammatory and pro-fibrotic signaling post-MI.
This Research Forward Project will pursue innovative mouse MI studies harnessing an engineered, WARF-patented ACE2 variant predicted to exhibit increased efficacy in HF with reduced side effects. ACE2 will also be tested for its ability to promote remuscularization of the failing heart by delivering ACE2 decorated human pluripotent stem cell-cardiomyocytes for enhancement of cell engraftment and survival. These experiments will open new avenues desperately needed for treatment of HF.