First gene therapy trial for heart failure begins in UK

An adenovirus vector is being used in the cardiac gene therapy trial run by Dr Alexander Lyon.

A clinical trial looking at whether gene therapy could help people with severe heart failure has started recruiting patients across Europe and in the United States. Dr Alexander Lyon, Cardiologist at The Physicians’ Clinic, who is a Consultant Cardiologist at The Royal Brompton Hospital, is the UK lead investigator. He has been widely quote in the media – see reports from BBC Health, The Guardian, The Telegraph, The Independent, Sky News and Channel 4 News. Here Dr Lyon explains some of the background to the trial, why it is being done, and how patients may benefit in the future.

“We are now treating UK patients for the first time to see if the gene therapy treatment can help repair their heart muscle. We have been studying this approach for over 20 years in our research laboratories at Imperial College, and it has now reached the second stage of assessment in individuals with heart failure. The CUPID 2 trial is an international trial across the USA and Europe, and follows on from the initial CUPID trial, which showed safety and some encouraging results treating heart failure patients in the USA with this novel therapeutic strategy” explains Dr Lyon.

Gene therapy and heart failure

People can develop heart failure after damage to the heart from a number of causes, including heart attacks, high blood pressure, inherited heart muscle disorders or after chemotherapy for cancer.

Dr Alexander Lyon

Dr Alexander Lyon

“We and our colleagues in the US have found that people with heart failure tend to have lower levels of a heart muscle protein responsible for pumping calcium around the cells which is critical for contraction and relaxation of the muscle with every heartbeat. This protein, known as sarcoplasmic reticulum calcium ATPase 2a (SERCA for short), is encoded by a gene in all of our heart muscle cells. In healthy hearts, this gene is active and generates sufficient levels of the SERCA protein to ensure strong contraction and rapid relaxation, regulating efficient heart function.”

Irrespective of the cause, the damaged heart paradoxically turns down or off this critical SERCA gene, leading to progressive fatigue and weakening of the heart muscle. As the heart fails, it cannot pump blood around the body efficiently and the individual may experience tiredness, shortness of breath and difficulty with walking and doing everyday tasks. They can even collapse because the electrical activity of the heart can become unstable, or stop leading to a cardiac arrest.

The cardiac gene therapy trial is a first for UK patients with heart failure

The cardiac gene therapy trial is a first for UK patients with heart failure

The gene therapy being tested in the CUPID 2 trial aims to introduce a copy of a normal SERCA gene into the heart muscle of patients who have an advanced form of heart failure. The DNA of the SERCA2a gene is delivered using an adeno-associated virus (AAV), which acts like a microscopic ‘courier’ to deliver the therapeutic DNA into the heart muscle cells. AAVs do not cause any known human disease, and in the small number of people to receive this treatment so far they appear safe. The solution containing the virus is injected directly into the coronary arteries via an angiogram. The viruses then naturally access the heart muscle cells. If it works, the new gene restores the levels of the SERCA2a protein, enabling their heart muscle cells to improve their calcium levels, stabilising function and hopefully the weakened heart becomes stronger and more efficient. However this is still in research trials, as the benefits need to be proven in a rigorous manner.

What is happening in the trial just now?

“We are working with other European and American cardiologists and we have started treating the first UK heart failure patients using gene therapy. The patients have been split into two groups – one will receive the gene therapy while the other will receive a placebo treatment. Neither we or the patient know who is receiving which treatment, as this could influence the results.”

The trial started in the UK earlier in 2013 and will continue until 2015, with results not expected until 2015/2016.

“Each patient will be followed for several years and we will be closely monitoring their progress, finding out if they feel better, if their ability to walk and their quality of life improves, and if they have less emergency admissions into hospital. Only then will we know whether SERCA2a gene therapy is a suitable and effective new treatment for individuals with heart failure.”