Researchers at hospitals in London and Glasgow plan to use an engineered virus to smuggle DNA into the heart in the first ever clinical trial of “gene therapy” for heart failure.
The technique, which has been 20 years in development, could help the 750,000 people in the UK living with heart failure.
The condition results from damage to the heart left over from a heart attack or side-effects of powerful chemotherapy drugs. After the heart is starved of oxygen, cells die and the remaining heart cells become fatigued.
“Once heart failure starts, it progresses into a vicious cycle where the pumping becomes weaker and weaker, as each heart cell simply cannot respond to the increased demand.” said Alex Lyon, a cardiologist at the Royal Brompton hospital in London who is leading the trial in the UK.
Our goal is to fight back against heart failure by targeting and reversing some of the critical molecular changes arising in the heart when it fails. Alex Lyon, cardiologist
“Our goal is to fight back against heart failure by targeting and reversing some of the critical molecular changes arising in the heart when it fails,” he said.
People with heart failure can find it difficult to walk long distances or climb stairs. The disease is usually progressive, with heart function gradually weakening over time. The only solutions are heart transplant or surgically implanted pumps to maintain blood flow.
The gene therapy adds a repair gene to failing heart cells which produces more of a protein called SERCA2a which regulates the availability of calcium in the heart. Without ample supplies of calcium, heart muscles are unable to contract properly or relax properly between contractions – two key symptoms of heart failure.
Tests on human cells in the laboratory at Imperial College in London and in animals have shown that the SERCA2a gene can be repaired, and reverses some of the symptoms of heart failure.
A US biotech company Celladon has patented a method for inserting the gene into human hearts. They are co-sponsoring the UK element of the trial along with the British Heart Foundation which funded much of the basic research involved.
The technique uses a harmless virus similar related to the common cold. The DNA from the virus is removed and replaced with SERCA2a gene. This virus is then injected into the heart where it infects heart cells. The cells’ own machinery then decodes the SERCA2a gene, making more of the calcium regulating protein that is missing in failing hearts.
“When the gene is repaired it produces more of the functional protein and the problem is reversed,” said Dr Lyon.
Early tests of the technique show it appears to be safe, now 200 patents with severe heart failure are being recruited in Europe and America to show that it is effective. Doctors in the UK want to recruit 10 or more patients into the trial here.
Not all heart failure patients may benefit, however. The virus used to insert the DNA is so common many patients may have antibodies to it, meaning their immune systems will destroy the virus before it can infect the heart cells.