Document Detail


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.
MedLine Citation:
PMID:  23137122     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Todd K Rosengart; Muath M Bishawi; Michael S Halbreiner; Mathew Fakhoury; Eileen Finnin; Charleen Hollmann; Annie Laurie Shroyer; Ronald G Crystal
Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-20
Journal Detail:
Title:  Human gene therapy     Volume:  24     ISSN:  1557-7422     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-20     Completed Date:  2013-09-10     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  203-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics,  metabolism*
Aged
Coronary Artery Bypass
Coronary Artery Disease / pathology,  therapy*
DNA, Complementary / genetics,  metabolism
Female
Follow-Up Studies
Genetic Therapy / methods*
Genetic Vectors / administration & dosage*
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Myocardial Ischemia
Thoracotomy / methods
Time Factors
Vascular Endothelial Growth Factor A / administration & dosage*
Grant Support
ID/Acronym/Agency:
R01HL085095/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A
Comments/Corrections

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