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Long Term Follow-up Assessment of a Phase I Trial of Angiogenic Gene Therapy Using Direct Intramyocardial Administration of an Adenovirus Vector Expressing the VEGF121 cDNA for the Treatment of Diffuse Coronary Artery Disease.
MedLine Citation:
PMID:  23137122     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aims: Based on studies in experimental animals demonstrating that AdVEGF121, an E1-E3- serotype 5 adenovirus coding for 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 yr) follow-up on these patients. Results: 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 mini-thoracotomy (Group B). There was no control group; the study participants served as the controls. The 5 and 10 year survival was 10/15 (67%) and 6/15 (40%) for the Group A patients, and 11/16 (69%) and 5/16 (31%) for Group B sole therapy patients, respectively. In comparison, maximal medical therapy in comparable groups in the literature have 3 to 5 yr 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. Conclusions: 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:
Eileen Finnin; Michael Halbreiner; Odelya Pagovich; Matthew Fakhoury; Todd Ronsengart; Muath Bishawi; Charleen Hollmann; Ronald Crystal
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  Human gene therapy     Volume:  -     ISSN:  1557-7422     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Stony Brook, United States; geneticmedicine8@med.cornell.edu.
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