Gene therapy for coronary restenosis: is the enthusiasm justified?

Despite dramatic technological advances in coronary intervention, restenosis following percutaneous coronary intervention remains an important cause of morbidity with major financial implications. By six months postprocedure, some 16–32% of highly selected patients receiving optimal treatment within the privileged context of a clinical trial have developed restenosis, necessitating target vessel revascularisation in 9–15% of patients. The development of antirestenotic treatments is therefore an area of intense research activity. The failure of conventional pharmacological agents to inhibit restenosis, along with concern over the long term safety and eYcacy of intracoronary brachytherapy, has fostered the belief that gene therapy may be the future of antirestenotic treatments. 3 Furthermore, the focal nature of restenosis makes it a highly attractive target for locally delivered genetic material that may have toxic eVects if administered systemically. However, the important question remains: can research in this field translate into clinically useful treatment or is our enthusiasm for antirestenotic gene therapy misplaced? There are two fundamental questions that must be answered before antirestenotic gene therapy may become a reality. Firstly, what genetic material should be delivered? We believe that current understanding of the pathogenesis of human restenosis is insuYcient to allow us to answer this question confidently. Secondly, and equally important, how should genetic material be delivered eVectively and safely?