Project Grant R01HL177305

Federal Project Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded The University of Iowa a $631,543 Project Grant under the Cardiovascular Diseases Research program (CFDA 93.837) on June 18, 2026, with completion scheduled for March 31, 2030. The research project focuses on developing novel gene therapies targeting junctophilin-2 (JP2) to treat heart failure with reduced ejection fraction. The principal deliverable is the advancement of adeno-associated virus (AAV) gene therapy platforms, specifically utilizing the optimized myoAAV system to express a calpain-resistant mutant of JP2 (JP2CR). This therapeutic approach aims to restore normal excitation-contraction coupling function in cardiomyocytes and suppress maladaptive transcriptional reprogramming that characterizes heart failure progression.

The funded research will generate scientific products including preclinical data demonstrating the efficacy of single myoAAV-JP2CR gene therapy in improving cardiac outcomes through sustained excitation-contraction coupling function. This work builds on preliminary findings from knock-in mouse models and prior adeno-associated virus expression studies, with the goal of translating fundamental mechanistic insights into a viable gene therapy intervention for a disease that currently has no cure. The University of Iowa, a major federal research institution with established expertise in cardiovascular research, will conduct the research at its Iowa City campus.