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Updated: Jun 18, 2026
Gene Transfer for Ischemic Heart Failure in a Preclinical Model
Published on: May 15, 2011
AAV9-cBIN1 gene therapy rescues chronic heart failure due to ischemic cardiomyopathy in a canine model
Muhammad S Khan1, Douglas Smego2, Jing Li1,3
1Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Insights
Gene therapy using AAV9-cBIN1 successfully reversed heart failure in dogs with ischemic cardiomyopathy. This novel treatment improved cardiac function and survival, offering hope for patients with heart failure.
Area of Science:
- Cardiovascular Medicine
- Gene Therapy
- Molecular Cardiology
Background:
- Ischemic cardiomyopathy leads to heart failure (HF), a major global health issue.
- Reduced cardiac bridging integrator 1 (cBIN1) function contributes to HF progression.
- Upregulating cBIN1 via gene therapy may restore cardiac function in HF.
Purpose of the Study:
- To investigate the efficacy of adeno-associated virus serotype 9 packaged cBIN1 (AAV9-cBIN1) gene therapy in a canine model of ischemic heart failure.
- To assess the potential of AAV9-cBIN1 to reverse cardiac dysfunction and improve survival.
Main Methods:
- Adult dogs with experimentally induced dilated cardiomyopathy and chronic heart failure (HF) were treated with AAV9-cBIN1 or AAV9-GFP gene therapy.
- Treatment involved a single series of endocardial injections when left ventricular ejection fraction (LVEF) dropped below 40%.
- Animals were monitored for 7 weeks using laboratory tests, echocardiography, and endocardial mapping.
Main Results:
- AAV9-cBIN1 treatment significantly improved LVEF (29% to 42%) and global longitudinal strain compared to controls.
- T-tubule morphology, left ventricular size, plasma biomarkers, and endocardial voltage were improved in the AAV9-cBIN1 group.
- Animals receiving AAV9-cBIN1 gene therapy survived the study period, unlike most control animals.
Conclusions:
- Low-dose AAV9-cBIN1 gene therapy effectively treats chronic heart failure resulting from ischemic cardiomyopathy.
- Myocardial-specific gene therapy can dramatically reverse HF progression.
- This approach holds promise for treating heart failure.
Background:
Ischemic cardiomyopathy and resultant heart failure (HF) is a significant cause of morbidity and mortality worldwide. Downregulation of cardiac bridging integrator 1 (cBIN1), a membrane scaffolding protein responsible for organizing t-tubules and organizing the calcium handing apparatus, occurs in progressive HF. Therefore, gene therapy upregulating cBIN1 production may rescue failing muscle and clinical HF.
Methods:
Adult mongrel dogs underwent ligation of the left anterior descending artery and developed progressive dilated cardiomyopathy and chronic HF. When left ventricular ejection fraction (LVEF) dropped below 40%, the animals received a one-time series of endocardial injections of either of low dose gene therapy composed of either adeno-associated virus serotype 9 packaged cBIN1 (AAV9-cBIN1, n = 6) or AAV9-GFP (green fluorescent protein, n = 4). Animals were followed up to 7 weeks after therapy delivery with laboratory, echocardiography, and endocardial mapping assessment.
Results:
Post injection of the negative control, animals develop progressive symptomatic HF requiring early termination of all but one animal prior to the end of the study. In contrast, the AAV9-cBIN1-treated group reveals a significant improvement in LV function, with a noticeable improvement in LVEF (29 ± 3% vs. 42 ± 2%, p = 0.0095) and global longitudinal strain (-7.1 ± 0.9% vs. -12.5 ± 1.6%, p = 0.0095). Compared to the control animals, the AAV9-cBIN1-treated group displays improved T-tubule morphology, left ventricular chamber size, plasma biomarkers, and endocardial voltage, and survives the study period.
Conclusions:
Chronic HF from ischemic cardiomyopathy can be successfully treated with low dose AAV9-cBIN1 gene therapy. This study indicates that myocardial specific therapy can dramatically reverse HF progression.
