Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease.

Publication Type	Review
Authors	Kaminsky S, Rosengart T, Rosenberg J, Chiuchiolo M, Van de Graaf B, Sondhi D, Crystal R
Journal	Hum Gene Ther
Volume	24
Issue	11
Pagination	948-63
Date Published	11/01/2013
ISSN	1557-7422
Keywords	Coronary Artery Disease, Coronary Vessels, Genetic Therapy, Neovascularization, Physiologic
Abstract	Cardiac gene therapy offers a strategy to treat diffuse coronary artery disease (CAD), a disorder with no therapeutic options. The use of genes to revascularize the ischemic myocardium has been the focus of two decades of preclinical research with a variety of angiogenic mediators, including vascular endothelial growth factor, fibroblast growth factor, hepatocyte growth factor, and others encoded by DNA plasmids or adenovirus vectors. The multifaceted challenge for developing efficient induction of collateral vessels in the ischemic heart requires a choice for route of delivery, dosing level, a relevant animal model, duration of treatment, and assessment of phenotype for efficacy. Overall, studies of gene therapy for ischemia in experimental models are very encouraging, with clear evidence of safety and efficacy, strongly supporting the concept that gene therapy to induce angiogenesis is a viable therapeutic approach for CAD. Clinical studies of cardiac gene therapy with angiogenic factors have added substantially to the evidence for efficacy, but definitive studies have not yet led to commercial approval. This review provides the general concepts for angiogenesis-based therapeutic approaches for diffuse CAD and summarizes the results from key studies in the field with recommendations for refinement to a successful product design and evaluation.
DOI	10.1089/hum.2013.2516
PubMed ID	24164242