Gene therapy trial begins in heart pump patients

A gene therapy trial has been launched to help people with advanced heart failure who must constantly carry a bulky battery to power an artificial heart pump.

The small pilot trial, led by Imperial College London and funded by the British Heart Foundation (BHF) and the Celladon Corporation, will involve 24 people living with the device, called a Left Ventricular Assist Device (LVAD). The trial is a subset of Celladon's CUPID Phase 2b trial, which is testing the therapy on 250 US and European patients with less advanced heart failure.

Around 100 people in UK are currently living with an LVAD, with around 80 people receiving the implant each year. The device helps restore normal blood flow and is given to people with advance heart failure or those who are at risk and waiting for a heart transplant.

The device requires two batteries (in case one fails) in a pack that can be worn over the shoulder or around the waist. 'It took some getting used to', says Lee Adams, a patient from Hertfordshire who uses an LVAD.

The aim of the therapy is to restore the heart's ability to beat by itself. Using a harmless modified virus as a gene carrier, the therapy is designed to increase levels of an enzyme involved in muscle contraction in damaged heart muscle cells. A lack of this enzyme is one of the mechanisms of heart failure.

The pressing need for alternative treatments is intensified by a shortage of organ donors in the UK. 'The rationale for this study is to investigate the effectiveness of a new form of therapy, which might in the future be a viable alternative to transplantation', says Dr Nick Banner, the consultant cardiologist at Harefield Hospital who performed the first gene therapy.

Professor Sian Harding, head of the BHF Centre of Regenerative Medicine at Imperial College London, and who helped develop the therapy, added: 'It's important to remember that the therapy is not correcting a gene defect. We are working much more downstream, which means that no matter what the cause of the heart failure, the therapy should be equally beneficial for patients whether their heart problems stem from genes, lifestyle or the environment or a mixture of all of these'.

A potential problem with this approach is that up to 60 percent of the population have immune system antibodies that target the natural form of the gene-transporting virus. The researchers will investigate whether this affects the treatment. CUPID has not yet trialled the therapy on patients who possess the virus antibodies.

'If we demonstrate that the antibody does not block the delivery of gene therapy, many more patients could benefit', says lead investigator Dr Alex Lyon, from the Royal Brompton and Harefield NHS Foundation Trust.

Adams is cautiously optimistic. 'The best thing that could happen would be for my heart function to show signs of improvement and for the gene therapy to prove to be a "miracle cure" for myself and other patients', he said.

'But I'm not building up my hopes too much because, for all I know, I might have had the placebo'.