April 1, 2012
Molecular targets in heart failure gene therapy: current controversies and translational perspectives
Key Result
Gene therapy for heart failure targets calcium handling proteins like SERCA2a, phospholamban, and ryanodine receptor, as well as cAMP signaling and microRNAs, offering novel translational potential.
Structured PICO
P
Population
Heart failure
I
Intervention
Gene therapy targeting calcium handling (SERCA2a, phospholamban, S100A1, ryanodine receptor, inhibitor of protein phosphatase 1), cAMP signaling (adenylyl cyclase), and microRNAs
This review highlights emerging molecular targets for heart failure gene therapy, particularly those related to calcium handling and cAMP signaling, which offer novel therapeutic avenues beyond traditional pharmacologic modulation.
Abstract
Use of gene therapy for heart failure is gaining momentum as a result of the recent successful completion of phase II of the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, which showed clinical safety and efficacy of an adeno-associated viral vector expressing sarco-endoplasmic reticulum calcium ATPase (SERCA2a). Resorting to gene therapy allows the manipulation of molecular targets not presently amenable to pharmacologic modulation. This short review focuses on the molecular targets of heart failure gene therapy that have demonstrated translational potential. At present, most of these targets are related to calcium handling in the cardiomyocyte. They include SERCA2a, phospholamban, S100A1, ryanodine receptor, and the inhibitor of the protein phosphatase 1. Other targets related to cAMP signaling are reviewed, such as adenylyl cyclase. MicroRNAs are emerging as novel therapeutic targets and convenient vectors for gene therapy, particularly in heart disease. We propose a discussion of recent advances and controversies in key molecular targets of heart failure gene therapy.