Data from: BacNav Gene Therapy Improves Function of Infarcted Engineered Human Myocardium and NHPs

This dataset contains the data used to generate the central figure in the associated publication. Background: Current clinical therapies for myocardial infarction and sudden cardiac death show limited efficacy. The ability to enhance amplitudes of sodium (Na+) current and calcium (Ca2+) transient in cardiomyocytes could uniquely restore both electrical and contractile deficits in infarcted cardiac tissue to prevent arrhythmias and improve pumping function of the heart.

Methods: The effects of BacNav expression were studied in an in vitro ischemia-reperfusion (I/R) model of engineered heart tissues (EHTs) made from human induced pluripotent stem cell-derived CMs (hiPSC-CMs). Further preclinical evaluations of CM-specific, adeno-associated virus (AAV)-mediated BacNav therapy were conducted in a nonhuman primate (NHP) model of myocardial infarction (MI).

Results: Our studies show that BacNav expression effectively rescues I/R-induced force decline and calcium mishandling in hiPSC-CM EHTs. Furthermore, AAV9-mediated BacNav gene therapy rescues contractile deficit (ejection fraction) and prevents arrhythmias in the settings of acute MI in NHPs. Importantly, this one-time intramyocardial delivery of AAV9-BacNav led to strong, sustained, localized CM-specific channel expression without causing any adverse effects.

Conclusions: We present a novel gene therapy that simultaneously targeting both electrical and contractile dysfunction of post-MI heart. These preclinical studies support the promise of BacNav gene delivery as an effective therapeutic strategy for providing both inotropic and antiarrhythmic benefits to the failing heart.