Getting to the heart of vein graft success: Professors Andrew Baker and Colin Berry

Issued: Wed, 26 Jun 2013 15:21:00 BST

The University is currently at the centre of a groundbreaking £3.9m project to develop gene therapy to prevent heart bypass graft failure. With funding from the Medical Research Foundation and British Heart Foundation, the team at the Institute of Cardiovascular & Medical Sciences is working towards a first-in- human trial at the Golden Jubilee National Hospital. Glasgow Professors Andrew Baker (principal investigator) and Colin Berry (trial chief investigator) lead the team.

When Professor Baker first started working in this area, at Cardiff University in 1995, many hundreds of thousands of coronary artery bypass grafts were performed using saphenous veins. The failure rate of this approach was very high, with 40–50% of grafts failing within ten years and no simple drug approaches available to improve patients’ prospects.

‘The beauty of the vein graft is that you have access to the tissue after it has been harvested from the leg and before it’s grafted into the coronary circulation,’ explains Professor Baker. ‘We’ve designed a gene therapy approach based on adenoviruses, which are sufficiently capable of manipulating the graft during that brief clinical window. Once the graft is put into the circulation, the virus starts to express a therapeutic gene called TIMP-3. This prevents the sort of adverse remodelling that we’ve seen can cause blockages.’

The virus has been used in many different clinical trials before, particularly in cancer but also in cardiovascular disease. It has a very good safety record, and in the current therapy it will be used in a moderate dose. Work is under way to create a clinical grade virus, and Professor Berry has initiated the applications for the clinical study, hoping to begin in the latter part of 2013.

Glasgow is the ideal location for such a trial. ‘The Golden Jubilee National Hospital is one of the largest integrated cardiothoracic centres in Europe,’ says Professor Berry. ‘It has a very large programme of coronary artery bypass surgery. The first-in-human trial is phase one of two; if it plays out well, we’ll move into phase two, which involves assessments for efficacy as well as safety.’

The team is now almost one year into the fiveyear programme, with each milestone passed taking them one step nearer to a safe and effective new treatment. There are opportunities for non-clinical and clinical PhDs to be involved in both this and other exciting programmes of research going on at the institute. ‘The environment created by the University, British Heart Foundation and NHS is perfect for translational research,’ says Professor Baker. ‘You get strength in individual areas – such as cancer, cardiovascular, immunology – and also interdisciplinary approaches to science. Students have lots of interactions with industry, including placements. It’s a fantastic place to work.’