The World Health Organisation (WHO) has predicted that by 2020 ischemic heart disease will be the world's most prolific cause of ill health. Song Wan, Associate Professor in the Department of Surgery at the Chinese University of Hong Kong, understands the urgency to find appropriate treatment for this type of heart disease.

A diseased heart that lacking adequate blood supply is generally treated in one of two ways – via stent implantation or with a coronary artery bypass grafting (CABG) operation which encompasses a degree of risk in terms of vein graft failure. Dr Wan as a member of an international collaborative research group drawn from the universities of Bristol, Glasgow and Yale has focused on the application of gene therapy to prevent vein graft failure.

CABG, in its classical application, involves the harvesting of one artery and two pieces of vein. All three are grafted on to the heart to replace some blocked coronary arteries in a single operation.

This process however has a degree of post-operative vulnerability with the vein, in the medium and long term, often unable to handle the heavier work load of an artery resulting in thrombosis, vascular lesions and eventually blockage again ("restenosis"). Ten or 15 years after the initial CABG operation, the same patient may require further surgery to bypass the blockage or mitigate other damage.

Drugs can be administered to prevent vein graft failure but, as Dr Wan says, there is to date no magic answer to grafted vein degeneration. He and his team have focused on the potential of gene therapy. The process they have designed and trialled successfully on pigs involves harvesting the vein from the leg of the animal, and treating it with certain genes, cleaning it and then transplanting it onto the heart. The treatment process takes just 30 minutes and the gene therapy appears to prevent the formation of neointima, a thickening of the vein walls. The treated vein maintains a clear lumen to take on the work of the artery and the risk for developing new blockage appears much reduced. One of the genes being tested so far, namely P53, has been successfully used in oncology treatment on humans.

The research which began with Research Grants Committee funding is currently jointly supported by the British Heart Foundation.

"In our experiments on pigs, gene therapy has significantly reduced neointima formation in both arterial and venous models of vascular injury and has the real potential of preventing post-angioplasty arterial restenosis or vein graft failure following coronary artery bypass grafting," Dr Wan says.

The current study will be completed in late 2009. As long as the evidence continues to support the theory, the group hope to then begin clinical work on patients. Studies on the long-term impacts of this therapy on humans may require a solid 15-20 year study period.

"We are very confident that we are on the right path with this," says Dr Wan. "The use of gene therapy in this manner will have major economic implications in terms of health care costs and the prevention of ongoing heart disease."

Dr Song Wan
Department of Surgery
The Chinese University of Hong Kong
swan@cuhk.edu.hk