VEGF gene transfer to prevent coronary artery restenosis

VEGF基因转移预防冠状动脉再狭窄

• 批准号: 6661529
• 负责人: DOUGLAS W LOSORDO
• 金额: $ 20.93万
• 依托单位: STEWARD ST. ELIZABETH'S MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6661529
• 关键词: angiocardioultrasonography; angiography; atherosclerosis; cardiovascular disorder therapy; clinical trials; coronary artery; gene therapy; human subject; human therapy evaluation; intraluminal angioplasty; patient oriented research; perfusion; restenosis; vascular endothelial growth factors; vascular endothelium

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.

该建议旨在研究为VEGF-1（VEGFA）基因的165-氨基酸同工型编码裸DNA的动脉基因转移，作为PTCA的辅助。该提案具有以下三个具体目标。具体目的1：确定经皮易感性冠状动脉血管成形术（PTCA）（PTS）（PTS）（PTS）（PTS）（PTS）（PTS）（PTS）（PTS）（PTS）的冠状基因转移对加速再内皮化（RET）的安全性。具体目的＃2：获得有关PHVEGF165冠状基因转移的生物活性的初步数据，以预防重述。具体目的＃3：确定PhVEGF165冠状基因转移对涉及PTCA靶位部位以外的冠状动脉部位的动脉粥样硬化进展的影响。基因转移后，在这项研究的患者中将进行各种评估。将进行串行临床检查 - 包括标准历史记录和体格检查 - 将进行标准实验室测试，以记录PHVEGF165冠状动脉基因转移的安全性。通过非侵入性测试（包括核灌注扫描，包括核灌注扫描）和侵入性测试），将进一步监测患者的状态。这些后一种检查对于解决特定目标2和3的问题将特别重要。这是我们的期望，即本研究的发现应建立安全性，并有可能提供有关功效的见解 - 这将有助于指导有关在II期试验中进一步测试该提出的治疗策略的决策价值。