Long-term follow-Up assessment of a phase 1 trial of angiogenic gene therapy using direct intramyocardial administration of an adenoviral vector expressing the VEGF121 cDNA for the treatment of diffuse coronary artery disease

Todd K. Rosengart, Muath M. Bishawi, Michael S. Halbreiner, Mathew Fakhoury, Eileen Finnin, Charleen Hollmann, Annie Laurie Shroyer, Ronald Crystal

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

On the basis of studies in experimental animals demonstrating that AdVEGF121, an E1-E3- serotype 5 adenovirus coding the 121 isoform of vascular endothelial growth factor (VEGF), could mediate the generation of new blood vessels and reverse coronary ischemia, a clinical study of direct myocardial administration of AdVEGF121 was initiated in patients with late-stage, diffuse coronary artery disease. This study provides long-term (median, 11.8 years) follow-up on these patients. From 1997 to 1999, AdVEGF121 was administered by direct myocardial injection to an area of reversible ischemia in 31 patients with severe coronary disease, either as an adjunct to conventional coronary artery bypass grafting (group A) or as minimally invasive sole (MIS) therapy, using a minithoracotomy (group B). There was no control group; the study participants served as the control subjects. The 5-and 10-year survival was 10 of 15 (67%) and 6 of 15 (40%) for the group A patients, and 11 of 16 (69%) and 5 of 16 (31%) for group B sole therapy patients, respectively. In comparison, maximal medical therapy in comparable groups in the literature have a 3-to 5-year survival rate of 52 to 59%. For the survivors, the angina score for group A was 3.4±0.5 at time 0 and 1.9±1.0 at last follow-up, and for group B it was 3.4±0.6 and 2.0±1.1, respectively. The incidences of malignancy and retinopathy were no greater than that expected for the age-matched general population. We conclude that adenovirus-mediated VEGF direct myocardial administration to patients with severe coronary artery disease is safe, and future larger trials are warranted to assess efficacy.

Original languageEnglish
Pages (from-to)203-208
Number of pages6
JournalHuman Gene Therapy
Volume24
Issue number2
DOIs
Publication statusPublished - 1 Feb 2013
Externally publishedYes

Fingerprint

Genetic Therapy
Coronary Artery Disease
Complementary DNA
Adenoviridae
Vascular Endothelial Growth Factor A
Therapeutics
Ischemia
Coronary Artery Bypass
Coronary Disease
Blood Vessels
Survivors
Protein Isoforms
Survival Rate
Control Groups
Injections
Survival
Incidence
Population
Neoplasms

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Long-term follow-Up assessment of a phase 1 trial of angiogenic gene therapy using direct intramyocardial administration of an adenoviral vector expressing the VEGF121 cDNA for the treatment of diffuse coronary artery disease. / Rosengart, Todd K.; Bishawi, Muath M.; Halbreiner, Michael S.; Fakhoury, Mathew; Finnin, Eileen; Hollmann, Charleen; Shroyer, Annie Laurie; Crystal, Ronald.

In: Human Gene Therapy, Vol. 24, No. 2, 01.02.2013, p. 203-208.

Research output: Contribution to journalArticle

Rosengart, Todd K. ; Bishawi, Muath M. ; Halbreiner, Michael S. ; Fakhoury, Mathew ; Finnin, Eileen ; Hollmann, Charleen ; Shroyer, Annie Laurie ; Crystal, Ronald. / Long-term follow-Up assessment of a phase 1 trial of angiogenic gene therapy using direct intramyocardial administration of an adenoviral vector expressing the VEGF121 cDNA for the treatment of diffuse coronary artery disease. In: Human Gene Therapy. 2013 ; Vol. 24, No. 2. pp. 203-208.
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