A clinical trial of gene therapy for heart failure

Investigation of the safety and feasibility of SERCA gene transfer in the human failing heart using an adeno-associated viral vector

Drugs can slow the progress of heart failure, but at present the only cure is a heart transplant, which is limited by the supply of donor hearts. Professor Sian Harding at Imperial College, London has shown that in the failing heart, even the seemingly undamaged portions of muscle are not functioning as well as they should. This suggests that the heart could be helped to pump more effectively by stimulating the undamaged muscle. Further research suggested that the underlying problem in the muscle was to do with the way the cells handle calcium. Each beat of the heart is triggered by the release of calcium from storage compartments inside the muscle cells. The amount of calcium that is released determines how strongly the muscle contracts. At the end of the beat, calcium is loaded back into the stores through a protein called SERCA2a. This allows the heart to relax and ensures that there is calcium ready to be released for the next heartbeat. In heart failure, SERCA2a doesn’t work as well as it should, which means that the heart doesn’t relax fully and it has less calcium stored in the cells. This is an important reason why the heart can’t pump very hard. Professor Harding has shown that using a virus to introduce new copies of the gene for SERCA2a can improve heart muscle function in human heart cells grown in a dish, as well as in live mice. Her team will now carry out a clinical trial in eight patients with heart failure to test whether this gene therapy is safe and feasible as a treatment option. If successful, the study will lead to larger trials, and may eventually provide doctors with a revolutionary new treatment for heart failure