Gene Therapy of Restenosis

Promise and Perils

Correspondence to Peter Libby, MD, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. E-mail plibby@rics.bwh.harvard.edu

Key Words: genetherapy • restenosis • vectors

The advent of technology for vascular gene transfer some 8 years ago led to an explosion of interest in the notion that local gene therapy could modify the natural history of arterial hyperplastic diseases.^{1 2} What better testing ground for this concept than restenosis following percutaneous transluminal coronary angioplasty (PTCA) or other arterial interventions? In this situation, the precise moment of onset of the pathological process, an iatrogenic arterial injury, is known. Furthermore, the site of the intervention predicts exactly where subsequent pathologies will develop. Finally, this very segment of the vasculature is instrumented at the time the pathological process commences.

A host of promising studies in animals has fueled enthusiasm for treatment of human restenosis by gene therapy. Various strategies, ranging from inhibition of genes involved in the cell cycle with antimetabolites to overexpression of nitric oxide synthase, have yielded reductions in intimal thickening after injury in experimental animals. The now widespread implantation of stents in diseased arteries provides further opportunity for transfer of nucleic acids or even genetically modified cells.

In view of these advances, are we at the threshold of a halcyon era of vascular intervention, or do obstacles remain that may frustrate the rapid application of these existing advances to patients? This issue is debated by the point/counterpoint articles in this issue (DeYoung & Dichek³ ; Baek & March⁴ ). This editorial aims to highlight the importance of this debate and also emphasize some potential problems that require consideration as application of recent advances in gene transfer . . . [Full Text of this Article]

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