Details

Autor(en) / Beteiligte

• ROSENGART, T. K
• LEE, L. Y
• HAHN, R. T
• DEVEREUX, R. B
• POST, M. R
• HACKETT, N. R
• FOSTER, T
• GRASSO, T. M
• LESSER, M. L
• ISOM, O. W
• CRYSTAL, R. G
• PATEL, S. R
• SANBORN, T. A
• PARIKH, M
• BERGMAN, G. W
• HACHAMOVITCH, R
• SZULC, M
• KLIGFIELD, P. D
• OKIN, P. M

Titel

Angiogenesis gene therapy : Phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease

Ist Teil von

• Circulation (New York, N.Y.), 1999-08, Vol.100 (5), p.468-474

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.