New trials of gene therapy for heart failure are announced

BMJ 2013; 346 doi: (Published 30 April 2013) Cite this as: BMJ 2013;346:f2795
  1. Geoff Watts
  1. 1London

The British Heart Foundation has announced the launch of two new trials of gene therapy for heart failure. They represent the culmination of 20 years of laboratory research by staff at Imperial College London and the Royal Brompton Hospital, London, and will be the first of their kind carried out in the United Kingdom, the researchers said.

Alexander Lyon, a consultant cardiologist at the Royal Brompton and the UK lead investigator, emphasised that heart failure was a major problem. “In the UK alone we have somewhere between 750 000 and a million patients we know about. And there’s a 30% mortality in the first year.”

The therapy itself relies on the use of a modified adenovirus as a vector to insert a gene, SERCA2a, directly into the heart. SERCA2a plays a part in the control of calcium signalling in heart cells. Introducing extra copies of the gene into failing heart cells should, in theory, boost their activity.

Sian Harding, professor of cardiac pharmacology at Imperial, has studied the performance of individual myocytes in the laboratory and shown that a protein called SERCA can fail in its task of moving enough calcium through the cell.

“We’ve used an adenovirus to convey the gene for SERCA into myocytes from a failing human heart,” she said. “We put in a gene rather than the protein because a gene will keep on producing SERCA.” The technique restores the failing myocytes to normality.

The two trials are intended to find out whether laboratory success can be replicated in patients. One of the two, a double blind, multicentre, randomised trial called CUPID2, has just recruited its first patients. CUPID2 will assess the benefits of a single dose of gene therapy in some 200 patients with severe chronic heart failure who are already receiving the best currently available treatment. Half will receive an infusion of virus directly into the heart. The remainder will receive only a placebo infusion.

The second and smaller trial, SERCA-LVAD, will test the effects of the same therapy in 24 other heart failure patients fitted with left ventricular assist devices. Due to be started in the summer, this study will allow researchers to measure the quantity of the gene successfully introduced into the patients’ heart muscle: a direct assessment of the effectiveness of the viral vector.

CUPID1, a smaller and earlier safety trial carried out in the United States, already offers grounds for optimism. “It was well tolerated, with no adverse effects from the infusion process itself,” said Lyon. “There were also some signs that it might be having an effect on the heart failure. There were fewer deaths or requirements for an urgent transplant . . . and improvement in the symptoms and exercise capacity of the patients.”

Peter Weissberg, medical director of the British Heart Foundation, which is co-funding the trials, described them as “a great example of what used to be called bench to bedside medicine.”


Cite this as: BMJ 2013;346:f2795