Novel AAV Gene Therapy Reverses Heart Failure in Preclinical Model, Targeting Contractile and Electrical Deficits

NEW ORLEANS, LA — November 11, 2025 — Results presented today at the American Heart Association’s (AHA) Scientific Sessions 2025 in New Orleans discussed a preclinical study demonstrating the transformative potential of a prokaryotic voltage-gated sodium channel (BacNav) gene therapy to restore contractile strength and electrical stability in a rat model of chronic ischemia-reperfusion heart failure (HF).

The study hypothesized that the expression of BacNav, delivered via a specialized AAV vector, can simultaneously target sodium and calcium dysregulation in failing cardiomyocytes. Augmentation of peak sodium current and calcium transient amplitude represents a promising avenue to restore both electrical and contractile dysfunction in HF, an area where current therapy options remain limited to long-term management.

Gene therapy, and particularly the AAV delivery system, has been demonstrated as a robust strategy for targeting the pathophysiological mechanisms of HF to provide inotropic and anti-arrhythmic effects in HF with reduced ejection fraction (HFrEF). As such, this form of AAV gene therapy presents a potential curative option for the condition.

A Proactive AAV Approach

Initially, the functional effects of BacNav expression were investigated ex vivo. Preclinical evaluations of cardiomyocyte-specific AAV-mediated BacNav therapy were subsequently conducted in a mouse traverse aortic constriction (TAC) model of chronic HF. The BacNav payload, delivered by an AAV vector (or control AAV), was administered four weeks post-surgery.

The study concluded that the expression of BacNav, facilitated by the AAV vector, dose-dependently enhances Ca2+ transient amplitude and contractility of cardiomyocytes by modulating ion channel activity and increasing Ca2+ stores.

In vivo results for the AAV-delivered therapy were dramatic:

• AAV9-mediated BacNav therapy alleviated fibrotic and hypertrophic changes.
• The AAV therapy rescued contractile deficit (delta left ventricular ejection fraction (LVEF): -3.5% versus -17.0% for control AAV treated animals).
• It prevented arrhythmias (0% versus 56% in control AAV treated animals).

Furthermore, the BacNav AAV gene therapy conferred protective effects on pressure-overload induced dysregulation of the cardiac transcriptome.

Future Outlook

This preclinical study strongly supports the promise of AAV-delivered BacNav gene therapy as a novel approach for HFrEF. Key opinion leaders (KOLs) consistently report a desire for cardio-metabolic therapies that significantly improve long-term outcomes and are potentially curative. If translational research proves this AAV therapy efficacious in humans, GlobalData forecasts that BacNav gene therapy could open a first-in-class market for disease-modifying genetic interventions in severe HF, creating high-value opportunities for healthcare systems aiming to reduce the burden of heart failure.