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Current Gene Therapy

Eiditor-in-Chief

ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

Clinical Use of Intracoronary Gene Transfer of Fibroblast Growth Factor for Coronary Artery Disease

Author(s): W. F. Penny and H. Kirk Hammond

Volume 4 , Issue 2 , 2004

Page: [225 - 230] Pages: 6

DOI: 10.2174/1566523043346408

Price: $58

Abstract

Anginal symptoms due to myocardial ischemia continue to affect millions of patients despite ongoing improvements in the diagnosis and treatment of coronary artery disease. Revascularization therapy with percutaneous coronary interventions and coronary artery bypass graft surgery can be highly effective in eligible subjects, but many patients are suboptimal candidates due to various factors, which include diffuse vascular disease, poor ventricular function and failure of prior procedures. Introduction of vascular growth factors to the heart to promote angiogenesis and collateral vessel formation has emerged as an alternative strategy for the relief of myocardial ischemia in these patients. Early preclinical work demonstrated that gene transfer of fibroblast growth factor using an E1-deleted adenovirus vector via intracoronary injection could safely reverse stress-induced ischemic ventricular dysfunction with no discernible evidence of inflammatory response. The AGENT trial established that intracoronary administration of Ad5FGF-4 could be performed with reasonable safety to patients with coronary artery disease, and that a one-time dose could provide an anti-ischemic effect out to 12 weeks of evaluation. Further evaluation of the efficacy and safety of Ad5FGF-4 is now being conducted in two simultaneous multicenter, randomized, double-blind, placebo-controlled pivotal trials in the United States and the European Union, with planned enrollment of ∼1000 treated subjects. The primary efficacy variable in the trial will be changed in treadmill exercise duration at 12 weeks compared to baseline. Secondary efficacy variables include the rate of all-cause mortality and coronary events (non-fatal myocardial infarction, and unplanned hospitalization and revascularization due to myocardial ischemia) up to 1 year.

Keywords: angiogenesis, gene therapy, adenovirus, fibroblast growth factor, myocardial ischemia


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