Rosengart T K, Lee L Y, Patel S R, Sanborn T A, Parikh M, Bergman G W, Hachamovitch R, Szulc M, Kligfield P D, Okin P M, 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
Department of Cardiothoracic Surgery, Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY, USA.
Circulation. 1999 Aug 3;100(5):468-74. doi: 10.1161/01.cir.100.5.468.
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.
治疗性血管生成是一种治疗血管功能不全的新实验策略，它通过给予已知在胚胎发育中诱导血管发育的介质来诱导缺血成年组织的新生血管形成。本报告总结了一项基因治疗策略的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）VEGF121.10）在具有临床显著意义的冠状动脉疾病患者的心肌中诱导治疗性血管生成。
通过直接心肌内注射将Ad（GV）VEGF121.10给予21例患者，注射到可逆性缺血区域，作为传统冠状动脉搭桥术的辅助治疗（A组，n = 15）或通过小切口开胸作为单一治疗（B组，n = 6）。没有证据表明与载体给药相关的全身性或心脏相关不良事件。在两组中，治疗后30天的冠状动脉造影和应激心肌灌注显像评估显示载体给药区域有改善。所有患者在治疗后心绞痛分级均有改善。在仅采用基因转移治疗的B组中，平板运动评估表明大多数患者有改善。
数据与以下概念一致，即对具有临床显著意义的冠状动脉疾病患者直接心肌内给予Ad（GV）VEGF121.10似乎耐受性良好，有必要启动该疗法的II期评估。
