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Gene therapy for coronary restenosis: is the enthusiasm justified?
  1. M O'Sullivan,
  2. M R Bennett
  1. Division of Cardiovascular Medicine, University of Cambridge Department of Medicine, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK
  1. Dr M O'Sullivanmo222{at}

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Despite dramatic technological advances in coronary intervention, restenosis following percutaneous coronary intervention remains an important cause of morbidity with major financial implications.1 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 efficacy of intracoronary brachytherapy, has fostered the belief that gene therapy may be the future of antirestenotic treatments.2 ,3 Furthermore, the focal nature of restenosis makes it a highly attractive target for locally delivered genetic material that may have toxic effects 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 insufficient to allow us to answer this question confidently. Secondly, and equally important, how should genetic material be delivered effectively and safely?

Targets for gene therapy


Many of the proposed targets for antirestenotic gene therapy have arisen from study of the effects of vascular injury in animals. Myriad papers report delivery of various transgenes that suppress the response to experimental vascular injury. This often leads to the postulate that a similar strategy would limit human restenosis. However, for such “gene therapies” to be useful in humans, the animal vascular injury and human percutaneous coronary intervention must produce similar physical insult to the vascular wall and provoke a similar injury response. Unfortunately, we …

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