AAV1/SERCA2a gene therapy did not improve the time to recurrent cardiovascular events compared to placebo in patients with severe heart failure in the CUPID2 trial.
Gene therapy targeting angiogenesis and calcium cycling remains a promising but challenging alternative therapy for heart failure, requiring further optimization of vectors and delivery methods.
Abstract Heart failure is the leading cause of hospitalization globally, burdening healthcare systems and the economy. Heart failure is a multifactorial cardiac syndrome, where the heart fails to maintain sufficient cardiac output to support body function. As the population ages, heart failure rates will increase. Current treatments, such as medications and surgery, are not suitable for all patients, creating a need for alternative therapies. Gene therapy offers promising new approaches, with therapeutic angiogenesis, regenerative strategies, and calcium ion regulation as key targets. SERCA2a plays a critical role in calcium regulation, and clinical trials have focused on its potential as a therapeutic agent. VEGF-B, which specifically targets the myocardium, also regulates myocardial metabolism and SERCA2a activity. Although clinical trials have been conducted, results have not consistently replicated pre-clinical success. This review summarizes the current state of gene therapy for heart failure, including therapeutic agents, vectors, delivery methods, and preclinical models. Graphical Abstract
Wang et al. (2026) conducted a review in Patients with severe heart failure (HFrEF) (n=250). AAV1/SERCA2a gene therapy vs. Placebo was evaluated on Time to recurrent cardiovascular events (including reduction in mortality and heart failure-related hospitalization). AAV1/SERCA2a gene therapy did not improve the time to recurrent cardiovascular events compared to placebo in patients with severe heart failure in the CUPID2 trial.
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