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 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
Externally publishedYes

Fingerprint

Genetic Therapy
Coronary Artery Disease
Hepatocyte Growth Factor
Fibroblast Growth Factors
Angiogenesis Inducing Agents
Therapeutics
Adenoviridae
Vascular Endothelial Growth Factor A
Myocardium
Plasmids
Theoretical Models
Ischemia
Animal Models
Phenotype
Safety
DNA
Research
Genes

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. (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

Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease. / Kaminsky, Stephen M.; Rosengart, Todd K.; Rosenberg, Jonathan; Chiuchiolo, Maria J.; Van De Graaf, Benjamin; Sondhi, Dolan; Crystal, Ronald.

In: Human Gene Therapy, Vol. 24, No. 11, 01.11.2013, p. 948-963.

Research output: Contribution to journalReview article

Kaminsky, SM, Rosengart, TK, Rosenberg, J, Chiuchiolo, MJ, Van De Graaf, B, Sondhi, D & Crystal, R 2013, 'Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease', Human Gene Therapy, vol. 24, no. 11, pp. 948-963. https://doi.org/10.1089/hum.2013.2516
Kaminsky SM, Rosengart TK, Rosenberg J, Chiuchiolo MJ, Van De Graaf B, Sondhi D et al. Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease. Human Gene Therapy. 2013 Nov 1;24(11):948-963. https://doi.org/10.1089/hum.2013.2516
Kaminsky, Stephen M. ; Rosengart, Todd K. ; Rosenberg, Jonathan ; Chiuchiolo, Maria J. ; Van De Graaf, Benjamin ; Sondhi, Dolan ; Crystal, Ronald. / Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease. In: Human Gene Therapy. 2013 ; Vol. 24, No. 11. pp. 948-963.
@article{ca1ba4b45e044713b28b44a435c010b7,
title = "Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease",
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.",
author = "Kaminsky, {Stephen M.} and Rosengart, {Todd K.} and Jonathan Rosenberg and Chiuchiolo, {Maria J.} and {Van De Graaf}, Benjamin and Dolan Sondhi and Ronald Crystal",
year = "2013",
month = "11",
day = "1",
doi = "10.1089/hum.2013.2516",
language = "English",
volume = "24",
pages = "948--963",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "11",

}

TY - JOUR

T1 - Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease

AU - Kaminsky, Stephen M.

AU - Rosengart, Todd K.

AU - Rosenberg, Jonathan

AU - Chiuchiolo, Maria J.

AU - Van De Graaf, Benjamin

AU - Sondhi, Dolan

AU - Crystal, Ronald

PY - 2013/11/1

Y1 - 2013/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84886791503&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886791503&partnerID=8YFLogxK

U2 - 10.1089/hum.2013.2516

DO - 10.1089/hum.2013.2516

M3 - Review article

C2 - 24164242

AN - SCOPUS:84886791503

VL - 24

SP - 948

EP - 963

JO - Human Gene Therapy

JF - Human Gene Therapy

SN - 1043-0342

IS - 11

ER -