Angiogenesis gene therapy

Phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease

Todd K. Rosengart, Leonard Y. Lee, Shailen R. Patel, Timothy A. Sanborn, Manish Parikh, Geoffrey W. Bergman, Rory Hachamovitch, Massimiliano Szulc, Paul D. Kligfield, Peter M. Okin, Rebecca T. Hahn, Richard B. Devereux, Martin R. Post, Neil R. Hackett, Taliba Foster, Tina M. Grasso, Martin L. Lesser, O. Wayne Isom, Ronald Crystal

Research output: Contribution to journalArticle

571 Citations (Scopus)

Abstract

Background - Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1-E3- adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. Methods and Results - Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n = 15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. Conclusions - The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Original languageEnglish
Pages (from-to)468-474
Number of pages7
JournalCirculation
Volume100
Issue number5
DOIs
Publication statusPublished - 3 Aug 1999
Externally publishedYes

Fingerprint

Adenoviridae
Genetic Therapy
Coronary Artery Disease
Complementary DNA
Therapeutics
Blood Vessels
Exercise Therapy
Coronary Angiography
Coronary Artery Bypass
Genes
Embryonic Development
Myocardium
Ischemia
Injections

Keywords

  • Angiogenesis
  • Coronary disease
  • Gene therapy
  • Genetics
  • Ischemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Angiogenesis gene therapy : Phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. / Rosengart, Todd K.; Lee, Leonard Y.; Patel, Shailen R.; Sanborn, Timothy A.; Parikh, Manish; Bergman, Geoffrey W.; Hachamovitch, Rory; Szulc, Massimiliano; Kligfield, Paul D.; Okin, Peter M.; Hahn, Rebecca T.; Devereux, Richard B.; Post, Martin R.; Hackett, Neil R.; Foster, Taliba; Grasso, Tina M.; Lesser, Martin L.; Isom, O. Wayne; Crystal, Ronald.

In: Circulation, Vol. 100, No. 5, 03.08.1999, p. 468-474.

Research output: Contribution to journalArticle

Rosengart, TK, Lee, LY, Patel, SR, Sanborn, TA, Parikh, M, Bergman, GW, Hachamovitch, R, Szulc, M, Kligfield, PD, Okin, PM, Hahn, RT, Devereux, RB, Post, MR, Hackett, NR, Foster, T, Grasso, TM, Lesser, ML, Isom, OW & Crystal, R 1999, 'Angiogenesis gene therapy: Phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease', Circulation, vol. 100, no. 5, pp. 468-474. https://doi.org/10.1161/01.CIR.100.5.468
Rosengart, Todd K. ; Lee, Leonard Y. ; Patel, Shailen R. ; Sanborn, Timothy A. ; Parikh, Manish ; Bergman, Geoffrey W. ; Hachamovitch, Rory ; Szulc, Massimiliano ; Kligfield, Paul D. ; Okin, Peter M. ; Hahn, Rebecca T. ; Devereux, Richard B. ; Post, Martin R. ; Hackett, Neil R. ; Foster, Taliba ; Grasso, Tina M. ; Lesser, Martin L. ; Isom, O. Wayne ; Crystal, Ronald. / Angiogenesis gene therapy : Phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. In: Circulation. 1999 ; Vol. 100, No. 5. pp. 468-474.
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abstract = "Background - Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1-E3- adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. Methods and Results - Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n = 15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. Conclusions - The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.",
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T2 - Phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease

AU - Rosengart, Todd K.

AU - Lee, Leonard Y.

AU - Patel, Shailen R.

AU - Sanborn, Timothy A.

AU - Parikh, Manish

AU - Bergman, Geoffrey W.

AU - Hachamovitch, Rory

AU - Szulc, Massimiliano

AU - Kligfield, Paul D.

AU - Okin, Peter M.

AU - Hahn, Rebecca T.

AU - Devereux, Richard B.

AU - Post, Martin R.

AU - Hackett, Neil R.

AU - Foster, Taliba

AU - Grasso, Tina M.

AU - Lesser, Martin L.

AU - Isom, O. Wayne

AU - Crystal, Ronald

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N2 - Background - Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1-E3- adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. Methods and Results - Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n = 15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. Conclusions - The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

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KW - Coronary disease

KW - Gene therapy

KW - Genetics

KW - Ischemia

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