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
Autor: | Michael S. Halbreiner, Shroyer Al, Eileen Finnin, Muath Bishawi, Mathew Fakhoury, Charleen Hollmann, Ronald G. Crystal, Todd K. Rosengart |
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Rok vydání: | 2013 |
Předmět: |
Male
Vascular Endothelial Growth Factor A medicine.medical_specialty DNA Complementary Time Factors Genetic enhancement Genetic Vectors Myocardial Ischemia Ischemia Coronary Artery Disease Kaplan-Meier Estimate Adenoviridae Coronary artery disease chemistry.chemical_compound Internal medicine Genetics medicine Humans Coronary Artery Bypass Molecular Biology Research Articles Aged business.industry Genetic Therapy Coronary ischemia Middle Aged medicine.disease Vascular endothelial growth factor Clinical trial Vascular endothelial growth factor A medicine.anatomical_structure Thoracotomy chemistry Cardiology Molecular Medicine Female business Follow-Up Studies Artery |
Zdroj: | Human Gene Therapy. 24:203-208 |
ISSN: | 1557-7422 1043-0342 |
Popis: | 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. |
Databáze: | OpenAIRE |
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