SF/HGF Gene Transfer for Peripheral Ischemia

描述(申请者提供)：心血管疾病居首位 美国致病和死亡原因，困扰5800多万人 美国人。血管生成因子可促进血管生成并改善 缺血时的血流灌注。散射因子/肝细胞生长因子(SF/HGF)可能是 由于对成分的多重作用而优于其他血管生成因子 血管生成级联反应和抗细胞凋亡的特性。我们的第一阶段研究 SF/HGF基因治疗大鼠和小鼠的治疗性血管生成 外周缺血模型。我们将通过以下方式确认和扩展这项工作 通过长期随访获得详细的剂量和时间进程信息 对小鼠的后肢既有治疗效果也有不良影响 缺血模型。我们还将研究SF/HGF基因治疗的好处 治疗衰老小鼠和糖尿病小鼠的外周缺血。这个 将采用兔外周缺血模型来评价补肾活血方的疗效 SF/HGF基因治疗的血流和后肢生理评价 侧支血管发育的灌流压力和解剖学评估， 毛细血管密度和肌肉萎缩。在其他研究中，我们将比较 SF/HGF基因治疗联合血管内皮细胞生长因子治疗的疗效这些项目的目标是 研究的目的是将SF/HGF基因治疗应用于临床。 建议的商业应用：不可用

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of morbidity and mortality in the US, afflicting over 58 million Americans. Angiogenic factors can increase vascularization and improve perfusion in ischemia. Scatter factor/hepatocyte growth factor (SF/HGF) may be superior to other angiogenic factors because of multiple actions on components of the angiogenic cascade and anti-apoptotic properties. Our Phase I studies demonstrated therapeutic angiogenesis by SF/HGF gene therapy in rat and mouse models of peripheral ischemia. We will confirm and extend this work by obtaining detailed dose and time course information with long-term follow-up for therapeutic benefit as well as adverse effects in the mouse hindlimb ischemia model. We will also examine the benefits of SF/HGF gene therapy in treating peripheral ischemia in aging mice and in mice with diabetes. The rabbit model of peripheral ischemia will be used to assess the effectiveness of SF/HGF gene therapy by physiological assessment of blood flow and hindlimb perfusion pressure and anatomical assessment of collateral vessel development, capillary density and muscle atrophy. In additional studies we will compare the effectiveness of SF/HGF gene therapy with VEGF therapy. The goal of these studies is to bring SF/HGF gene therapy to clinical practice. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE