Virus therapy could offer new hope for heart failure patients

Additional treatments are urgently needed to help improve survival and quality of life in patients with advanced heart failure. The left ventricular assist device (LVAD), an implantable mechanical pump, is often used as a bridge to transplant. Recent data have shown that recovery of cardiac muscle function is possible during LVAD support and some patients may be removed from the devices and lead normal lives.

Now cardiologists in the UK and the US plan to use a virus to transfer a gene (SERCA2a) known to produce changes in calcium handling mechanisms of the failing heart and thus to increase the strength of contraction. Down-regulation of SERCA2a is common to heart failure of various aetiologies, and has been conclusively linked to the poor relaxation and contraction of the failing human heart, especially at higher beating rates.

The trial will take place at Harefield and Papworth Hospitals, under the sponsorship of Imperial College. This first trial in the UK is to determine the safety and feasibility of giving a replication-deficient adeno-associated viral vector (AAV6) expressing SERCA2a, driven by the CMV promoter (AAV6-CMV-SERCA2a). The results will be assessed in conjunction a companion study which has already started in the US, which includes both a dose-ranging and placebo-controlled arm.

Administration will be performed by percutaneous placement of a catheter into the coronary arteries and infusion of vector in saline. Pre-clinical studies have confirmed the efficacy of AAV infection and gene transfer using the coronary delivery route. The patient population will be heart failure patients who are clinically stable after implantation of LVADs. The advantage of this patient population is that they are protected from the major potential cardiac risks, arrhythmias and deterioration of function, by the presence of the LVAD. Additionally, tissue can be obtained either when the patient is explanted, or when the pump is removed. This gives the potential for determining the efficacy in terms of viral transfection.

Presenting plans for this research, Prof. Sian E Harding
 of the National Heart and Lung Institute said that although the LVAD patient population has advantages in terms of safety and measures of tissue efficacy, the ultimate goal is to apply SERCA2a gene therapy to all suitable patients with heart failure.