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. Academic Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Aged, 80 and over
  • Combined Modality Therapy
  • Coronary Artery Bypass
  • DNA, Complementary
  • Exercise Test
  • Female
  • Humans
  • Injections
  • Male
  • Middle Aged
  • Myocardium
  • Severity of Illness Index
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

MeSH Major

  • Adenoviridae
  • Coronary Circulation
  • Coronary Disease
  • Endothelial Growth Factors
  • Genetic Therapy
  • Genetic Vectors
  • Lymphokines
  • Neovascularization, Physiologic

abstract

  • 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. 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. 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.

publication date

  • August 3, 1999

has subject area

  • Adenoviridae
  • Adult
  • Aged
  • Aged, 80 and over
  • Combined Modality Therapy
  • Coronary Artery Bypass
  • Coronary Circulation
  • Coronary Disease
  • DNA, Complementary
  • Endothelial Growth Factors
  • Exercise Test
  • Female
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Injections
  • Lymphokines
  • Male
  • Middle Aged
  • Myocardium
  • Neovascularization, Physiologic
  • Severity of Illness Index
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Research

keywords

  • Clinical Trial
  • Clinical Trial, Phase I
  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 10430759

Additional Document Info

start page

  • 468

end page

  • 474

volume

  • 100

number

  • 5