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
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
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DOI：
10.1161/01.cir.100.5.468
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发表时间：
1999-08-03
期刊：
影响因子：
37.8
通讯作者：
Crystal, RG
中科院分区：
文献类型：
--
作者：
Rosengart, TK;Lee, LY;Crystal, RG
背景-治疗性血管生成是治疗血管功能不全的一种新的实验策略，它使用已知在胚胎发生中诱导血管发育的介质来诱导：缺血性成人组织的新血管形成。本报告总结了基因治疗策略的I期临床经验，该策略使用表达人血管内皮生长因子（VEGF）121 cDNA的E1（-）E3（-）腺病毒（Ad）基因转移载体（Ad（GV）VEGF 121.10）在具有临床显著性的个体的心肌中诱导治疗性血管生成：方法和结果：21例患者通过直接心肌注射Ad（GV）VEGF 121.10至可逆性缺血区域，作为常规冠状动脉旁路移植术的辅助治疗，（A组，n=15）或作为通过小切口胸廓切开术的单一疗法（B组，n=6）。没有与载体施用相关的全身或心脏相关不良事件的证据。在两组中，治疗后30天的冠状动脉造影和室壁运动的负荷sestamibi扫描评估表明向量管理区域有所改善。所有患者均报告治疗后心绞痛分级改善。在组B，其中基因转移是唯一的治疗，跑步机运动评估建议改善在大多数individuals. Conclusions的数据是一致的概念，即直接心肌管理的Ad（GV）VEGF 121.10的个人有临床意义的冠状动脉疾病似乎是耐受性良好，和启动阶段LI评估这种疗法是必要的。
Background-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.Methods and Results-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. Tn 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.Conclusions-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 LI evaluation of this therapy is warranted.