Although angioplasty and coronary bypass grafting are commonly used to treat coronary heart disease, many patients are not candidates for these procedures. New treatments, such as """"""""therapeutic angiogenesis"""""""", in which growth factor proteins or genes are used to induce revascularization of ischemic myocardium, may provide the alternatives needed. In Phase I studies, we initiated development of gene therapy for revascularization. Vectors encoding the angiogenic gene basic fibroblast growth factor (FGF2) were formulated in collagen-based matrices, and when delivered to ischemic myocardium induced both neovascularization and restoration of myocardial contractility. We now propose to continue this work through advanced pre-clinical studies, designed to enable an IND submission and initiation of a Phase I clinical safety study.
Specific Aim #1 proposes to evaluate AdFGF2 in a collagen-gelatin matrix for its ability to improve myocardial contractility in a dose-escalating efficacy study.
Specific Aim #2 describes the development, scale-up and cGMP manufacture of bulk AdFGF2 to be utilized in pre-clinical and clinical studies.
Specific Aim #3 describes evaluating acute toxicology and biodistribution in response to AdFGF2 in collagen-gelatin. Data generated will establish comprehensive efficacy and safety data in animals.
