SERCA2a (gene therapy)

Class

AAV1-delivered SERCA2a gene therapy

SERCA2a is the pump protein embedded in the sarcoplasmic reticulum membrane of heart muscle cells that moves calcium out of the cytoplasm and back into this internal storage compartment after each heartbeat. This step is essential for the heart muscle to relax between contractions and to reload calcium for the next beat. In heart failure, SERCA2a levels and activity typically decline, contributing to weaker contractions, impaired relaxation, and susceptibility to abnormal heart rhythms. The therapeutic rationale is to restore SERCA2a function directly at its genetic source rather than modulating it pharmacologically. This is accomplished using a gene therapy approach: a modified, non-replicating adeno-associated virus (AAV) serves as a delivery vehicle, carrying a functional copy of the SERCA2a gene into heart muscle cells, where it can drive renewed protein production. The AAV1 serotype used here has a natural affinity for muscle tissue, making it a logical carrier for cardiac-directed delivery. This mechanism is broadly relevant to heart failure with reduced pump function, a condition in which the underlying calcium-handling defect is a shared feature across many patients, regardless of the original cause of cardiac injury. Unlike drugs that must be taken repeatedly, gene therapy aims for a single administration with durable, potentially long-lasting protein expression.