Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease

Stephen M. Kaminsky, Todd K. Rosengart, Jonathan Rosenberg, Maria J. Chiuchiolo, Benjamin Van De Graaf, Dolan Sondhi, Ronald G. Crystal

Research output: Contribution to journalReview article

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)948-963
Number of pages16
JournalHuman gene therapy
Volume24
Issue number11
DOIs
Publication statusPublished - 1 Nov 2013

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Kaminsky, S. M., Rosengart, T. K., Rosenberg, J., Chiuchiolo, M. J., Van De Graaf, B., Sondhi, D., & Crystal, R. G. (2013). Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease. Human gene therapy, 24(11), 948-963. https://doi.org/10.1089/hum.2013.2516