Scientists’ £3.9m project to develop gene therapy to prevent heart bypass graft failure
Issued: Mon, 15 Aug 2011 13:00:00 BST
A team of scientists, cardiologists and heart surgeons from the University of Glasgow and the Golden Jubilee National Hospital has been awarded £3.9m for a study into how to prevent the failure of heart bypass grafts.
The award was made by the Medical Research Council and British Heart Foundation (BHF) to a team at the University’s Institute of Cardiovascular and Medical Sciences led by Professor Andrew Baker.
Coronary artery bypass grafting is a common treatment for coronary artery disease and usually involves taking a piece of vein from the leg – the saphenous vein – and grafting it on to the diseased heart artery to bypass that section and improve blood flow.
There are more than 28,000 coronary artery bypass graft operations performed each year in the UK (NHS.uk Choices). The majority use saphenous veins but around 10 per cent of such grafts become blocked within a year, and more than a third are blocked within 10 years.
Bypass graft failure starts off with the growth of new cells in the vein which eventually cause it to narrow and block, preventing blood flow to the heart muscle.
The researchers hope to prevent this failure by delivering a modified virus into the saphenous vein in the operating theatre before it is implanted into the heart.
The virus is modified so it is unable to replicate, but instead expresses a specific therapeutic gene called TIMP-3 that inhibits undesired tissue growth. This gene has been shown to significantly reduce the formation of blockages in human saphenous veins in laboratory tests, and has been demonstrated to be an effective gene therapy following bypass procedures in relevant models of the disease.
Prof Baker said: “Given the heavy reliance on saphenous vein grafts for coronary artery bypass procedures, and bypass grafts becoming blocked in the long term, there is an obvious and urgent need to find a solution to this problem.
“This study will enable us to test the safety and efficacy of this new treatment and provide the data to support future studies in larger numbers of patients.”
The clinical trial will be carried out in the Golden Jubilee National Hospital, Clydebank, which is home to regional and national heart and lung services. The trial will be sponsored by NHS Glasgow Biomedicine.
Professor Colin Berry, Consultant Cardiologist at the Golden Jubilee National Hospital, will lead the clinical team. He said: "The phase one and phase two randomised controlled trials, involving 12 and 120 patients respectively, will assess the safety and efficacy of this approach in patients.
“The study therapy will be given during surgery and then state-of-the art vascular imaging techniques, such as optical coherence tomography, will be used one year after surgery to quantify vein graft disease."
Professor Keith Oldroyd, Director of Research and Development at the Golden Jubilee, added: “This major grant award from the British Heart Foundation and Medical Research Council has resulted from a close collaboration between clinicians and scientists in the University of Glasgow and the Golden Jubilee National Hospital.
“This is a very important study which, if positive, could lead to a significant improvement in the long term results of heart bypass surgery and therefore have a better outcome for our future patients.”
Professor Peter Weissberg, Medical Director at the BHF said: “More than 28,000 people have a heart bypass operation every year in the UK. Despite immediate improvement in the patient’s condition, over time the grafts often fail. This means heart patients may suffer a recurrence of symptoms and may need to undergo the trauma of repeat surgery.
“Through this joint MRC and BHF grant, Professor Baker and his team will carry out the first ever human trials of this kind of gene therapy. This trial is the culmination of 15 years work to understand what causes graft failure and make a virus that can deliver genes to bypass grafts to stop them becoming blocked. It is a true lab-to-patient project involving collaboration between laboratory scientists and clinical researchers.
“If these trials prove this therapy to be safe and effective, it will have a major impact on the long-term outcomes for heart bypass patients.”
The five-year study will involve Professor Andrew Baker (Principal Investigator) and co-investigators Professor Colin Berry (Trial Chief Investigator); Dr Stuart Nicklin; Dr Niko Tzemos; Professor Keith Oldroyd; Mr Geoff Berg; and Professor Ian Ford – many of whom work across the Golden Jubilee National Hospital, NHS Greater Glasgow and Clyde and the University of Glasgow.
Notes to Editors
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