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: 7123944
• 负责人: DOUGLAS W LOSORDO
• 金额: $ 22.81万
• 依托单位: STEWARD ST. ELIZABETH'S MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7123944
• 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.

本提案旨在研究编码VEGF-1（VEGF A）基因的165个氨基酸同种型的裸DNA作为PTCA辅助的动脉基因转移。该提案有以下三个具体目标。具体目标1：确定phVEGF 165的冠状动脉基因转移在患有狭窄或闭塞的天然冠状动脉的患者（pts）中加速经皮腔内冠状动脉成形术（PTCA）后的再内皮化（rET）的安全性。具体目标#2：获得关于phVEGF 165冠状动脉基因转移用于预防再狭窄的生物活性的初步数据。具体目标#3：确定phVEGF 165冠状动脉基因转移对涉及冠状动脉部位而非PTCA靶部位的动脉粥样硬化进展的影响。在基因转移后，将对入组本研究的患者进行各种评估。将进行一系列临床检查-包括标准病史和体格检查-以及标准实验室检查，以记录phVEGF 165冠状动脉基因转移的安全性。将通过非侵入性测试（运动前和运动后测试-包括核灌注扫描）和侵入性测试（定量冠状动脉病变和血管内超声前和后）进一步监测患者的状态。后两项审查对实现具体目标2和3特别重要。我们预计，这项研究的结果应该确定安全性-并可能提供有关疗效的见解-这将有助于指导有关在II期试验中进一步测试这种拟议治疗策略的价值的决策。