Intracoronary gene transfer of fibroblast growth factor in experimental and clinical myocardial ischemia

An animal model of stress-induced regional myocardial ischemia was used to test the hypothesis that intracoronary delivery of an adenovirus encoding fibroblast growth factor Type 5 (FGF5) would result in improved blood flow, function and neovascularization in the ischemic region of the heart. These data indicated that this approach could be used safely and effectively in resolving regional myocardial ischemia in the ameroid model. Additional unpublished studies confirmed that a similar effect was achievable through use of other angiogenic transgenes, including FGF Type 4 (FGF4). The published studies using direct intracoronary delivery of adenovirus vectors to the heart is reviewed, with a focus on safety and efficacy. A multicenter Phase 1/Phase 2 clinical trial of intracoronary delivery of FGF4 in patients with angina pectoris was initiated under joint sponsorship of Collateral Therapeutics, Incorporated, Berlex Biosciences and Schering AG. Results of this trial are reviewed. The results of this blinded and randomized clinical trial provided data supporting the initiation of two large scale pivotal clinical trials — in the European Union and the US — of intracoronary delivery of adenovirus encoding FGF4 in treating patients with angina.