This Proposal has been designed to investigate arterial gene transfer of naked DNA encoding for the 165-amino acid isoform of the VEGF-1 (VEGF A) gene as an adjunct to PTCA. The Proposal has the following three Specific Aims.
Specific Aim #1 : to determine the safety of coronary gene transfer of phVEGF165 to accelerate re-endothelialization (rET) following percutaneous transluminal coronary angioplasty (PTCA) in patients (pts) with stenotic or occluded native coronary arteries.
Specific Aim #2 : to obtain preliminary data regarding bioactivity of coronary gene transfer of phVEGF165 for prevention of restonosis.
Specific Aim #3 : to determine the impact of phVEGF165 coronary gene transfer on the progression of atherosclerosis involving coronary arterial sites other than PTCA target sites. A variety of assessments will be performed among the patients enrolled in this study following gene transfer. Serial clinical examinations- including standard history and physical examinations-along with standard laboratory tests will be performed to document the safety of phVEGF165 coronary gene transfer. The patients' status will be further monitored by both non-invasive tests (pre- and post-exercise testing-including nuclear perfusion scans) and invasive testing )pre- and post-quantitative coronary angiopathy and intravascular ultrasound). These latter examinations will be particularly critical for addressing Specific Aims 2 and 3. It is our anticipation that the findings of this study should establish the safety- and potentially provide insights regarding efficacy- that would help to guide decisions regarding the value of testing this proposed therapeutic strategy further in Phase II trials.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL066957-05
Application #
7123944
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2006-01-01
Budget End
2008-08-31
Support Year
5
Fiscal Year
2005
Total Cost
$228,075
Indirect Cost
Name
St. Elizabeth's Medical Center of Boston
Department
Type
DUNS #
073797292
City
Boston
State
MA
Country
United States
Zip Code
01235
Sekiguchi, Haruki; Ii, Masaaki; Jujo, Kentaro et al. (2013) Estradiol promotes neural stem cell differentiation into endothelial lineage and angiogenesis in injured peripheral nerve. Angiogenesis 16:45-58
Sekiguchi, Haruki; Ii, Masaaki; Jujo, Kentaro et al. (2012) Estradiol triggers sonic-hedgehog-induced angiogenesis during peripheral nerve regeneration by downregulating hedgehog-interacting protein. Lab Invest 92:532-42
Webber, Matthew J; Tongers, Jorn; Newcomb, Christina J et al. (2011) Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair. Proc Natl Acad Sci U S A 108:13438-43
Roncalli, Jerome; Renault, Marie-Ange; Tongers, Jorn et al. (2011) Sonic hedgehog-induced functional recovery after myocardial infarction is enhanced by AMD3100-mediated progenitor-cell mobilization. J Am Coll Cardiol 57:2444-52
Ii, Masaaki; Takeshita, Kyosuke; Ibusuki, Kayoko et al. (2010) Notch signaling regulates endothelial progenitor cell activity during recovery from arterial injury in hypercholesterolemic mice. Circulation 121:1104-12
Webber, Matthew J; Tongers, Jörn; Renault, Marie-Ange et al. (2010) Development of bioactive peptide amphiphiles for therapeutic cell delivery. Acta Biomater 6:3-11
Ii, Masaaki; Hoshiga, Masaaki; Negoro, Nobuyuki et al. (2009) Adrenal androgen dehydroepiandrosterone sulfate inhibits vascular remodeling following arterial injury. Atherosclerosis 206:77-85
Losordo, Douglas W; Kishore, Raj (2009) A big promise from the very small identification of circulating embryonic stem-like pluripotent cells in patients with acute myocardial infarction. J Am Coll Cardiol 53:10-2
Zhou, Junlan; Zhu, Yan; Cheng, Min et al. (2009) Regulation of vascular contractility and blood pressure by the E2F2 transcription factor. Circulation 120:1213-21
Ropper, Allan H; Gorson, Kenneth C; Gooch, Clifton L et al. (2009) Vascular endothelial growth factor gene transfer for diabetic polyneuropathy: a randomized, double-blinded trial. Ann Neurol 65:386-93

Showing the most recent 10 out of 29 publications