Six-month assessment of a phase I trial of angiogenic gene therapy for the treatment of coronary artery disease using direct intramyocardial administration of an adenovirus vector expressing the VEGF121 cDNA

Todd K. Rosengart, Leonard Y. Lee, Shailen R. Patel, Paul D. Kligfield, Peter M. Okin, Neil R. Hackett, O. Wayne Isom, Ronald Crystal

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

Objective: To summarize the 6-month follow-up of a cohort of patients with clinically significant coronary artery disease who received direct myocardial injection of an E1-E3- adenovirus (Ad) gene transfer vector (Ad(GV)VEGF121.10) expressing the human vascular endothelial growth factor (VEGF) 121 cDNA to induce therapeutic angiogenesis. Background: Therapeutic angiogenesis describes a novel approach to the treatment of vascular occlusive disease that uses the administration of growth factors known to induce neovascularization of ischemic tissues. Methods: Direct myocardial injection of Ad(GV)VEGF121.10 into an area of reversible ischemia was carried out in 21 patients as an adjunct to conventional coronary artery bypass grafting (group A, n = 15) or as sole therapy using a minithoracotomy (group B, n = 6). Results: No evidence of systemic or cardiac-related adverse events related to vector administration was observed up to 6 months after therapy. Trends toward improvement in angina class and exercise treadmill testing at 6-month follow-up in the sole therapy group suggest the effects of this therapy are persistent for ≥6 months. Conclusions: This study suggests that direct myocardial administration of Ad(GV)VEGF121.10 appears to be well tolerated in patients with clinically significant coronary artery disease. Initiation of phase II evaluation of this therapy appears warranted.

Original languageEnglish
Pages (from-to)466-472
Number of pages7
JournalAnnals of Surgery
Volume230
Issue number4
DOIs
Publication statusPublished - 1 Oct 1999
Externally publishedYes

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Adenoviridae
Genetic Therapy
Coronary Artery Disease
Complementary DNA
Therapeutics
Injections
Group Psychotherapy
Vascular Diseases
Coronary Artery Bypass
Intercellular Signaling Peptides and Proteins
Ischemia
Exercise
Genes

ASJC Scopus subject areas

  • Surgery

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Six-month assessment of a phase I trial of angiogenic gene therapy for the treatment of coronary artery disease using direct intramyocardial administration of an adenovirus vector expressing the VEGF121 cDNA. / Rosengart, Todd K.; Lee, Leonard Y.; Patel, Shailen R.; Kligfield, Paul D.; Okin, Peter M.; Hackett, Neil R.; Isom, O. Wayne; Crystal, Ronald.

In: Annals of Surgery, Vol. 230, No. 4, 01.10.1999, p. 466-472.

Research output: Contribution to journalArticle

Rosengart, Todd K. ; Lee, Leonard Y. ; Patel, Shailen R. ; Kligfield, Paul D. ; Okin, Peter M. ; Hackett, Neil R. ; Isom, O. Wayne ; Crystal, Ronald. / Six-month assessment of a phase I trial of angiogenic gene therapy for the treatment of coronary artery disease using direct intramyocardial administration of an adenovirus vector expressing the VEGF121 cDNA. In: Annals of Surgery. 1999 ; Vol. 230, No. 4. pp. 466-472.
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