First clinical trial of gene therapy to prevent graft failure post CABG

Gene therapy for vein graft failure (joint funding with MRC)

Doctors sometimes recommend coronary bypass surgery for people with coronary heart disease (CHD), to improve the blood supply to heart muscle. It involves taking an artery or vein from elsewhere in the body and grafting it into the coronary circulation, bypassing the narrowed artery. This surgery helps to relieve angina symptoms and improve the patient’s quality of life. Despite immediate improvement in the patient’s condition, over time the grafts using veins often fail. This failure is caused by an accelerated narrowing of the bypass graft, caused by creation and migration of smooth muscle cells in the vessel wall. Professor Baker and his colleagues (including Professor Sarah George, Bristol University and Dr Song Wan, Chinese University of Hong Kong) have successfully shown, in animals and human tissue in the lab, that gene therapy can be used to reduce the likelihood of a bypass vein graft failing. He will now take this treatment from the laboratory to patients. This gene therapy technique has been in development for the past 15 years. It involves delivering a protective gene into the cells in the wall of the bypass graft. The gene prevents the smooth muscle cells multiplying and moving into the centre of the vessel, which can cause narrowing and graft failure. The gene produces a protein called ‘tissue inhibitor of metalloproteinases-3’ (TIMP-3). It is delivered into the cells using a virus which cannot multiply but carries the TIMP-3 gene. There it tells the cells to manufacture more TIMP-3, which reduces their ability to proliferate and break away from their neighbours to migrate through the vessel wall. TIMP-3 is a natural human gene that boosts a normal process, keeping the health of the graft in check. Now Baker and his team will carry out the first human trials of this gene therapy. This funding will allow Professor Baker to carry out the vital first two phases of clinical trials – the first phase with just 12 patients and the second with 120-160. Eligible patient volunteers will receive the gene therapy during their surgery and then the effects of the treatment will be assessed after a fortnight, a month, and a year. If successful, this therapy could significantly improve the success of coronary bypass surgery and avoid the recurrence of symptoms or the need for another operation in thousands of patients each year.