Markkanen Johanna E, Rissanen Tuomas T, Kivelä Antti, Ylä-Herttuala Seppo
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, Kuopio, Finland.
Cardiovasc Res. 2005 Feb 15;65(3):656-64. doi: 10.1016/j.cardiores.2004.10.030.
Myocardial ischemia is one of the most promising targets of gene therapy. Although several growth factors and delivery approaches have yielded positive results in preclinical studies, first clinical studies have shown little or no real clinical benefit to the patients. It is likely that less than optimal gene therapy approaches have been used so far, and more thorough preclinical studies are needed in order to establish safe, efficient pro-angiogenic therapy. Growth factor, gene transfer vector, delivery method and target microenvironment need to be chosen based on the therapeutic target. It has become apparent that induction of large collateral arteries in the myocardium may need a different approach than rapid growth of neovasculature around infarction scar. Large animal models are necessary in the determination of optimal therapeutic agent, dose and clinically relevant delivery strategy.
心肌缺血是基因治疗最有前景的靶点之一。尽管几种生长因子和递送方法在临床前研究中取得了积极成果，但首批临床研究表明对患者几乎没有或没有真正的临床益处。很可能到目前为止使用的基因治疗方法并不理想，需要更全面的临床前研究以建立安全、有效的促血管生成疗法。生长因子、基因转移载体、递送方法和靶微环境需要根据治疗靶点来选择。显而易见的是，在心肌中诱导大的侧支动脉可能需要与梗死瘢痕周围新生血管快速生长不同的方法。大型动物模型对于确定最佳治疗药物、剂量和临床相关递送策略是必要的。
