SF/HGF Gene Transfer for Peripheral Ischemia

描述（由申请人提供）：心血管疾病是主要的 在美国的发病率和死亡率的原因，影响超过58万 美国人血管生成因子可以增加血管形成， 缺血再灌注。分散因子/肝细胞生长因子（SF/HGF）可以是 上级于其他血管生成因子，因为其对成分具有多重作用 血管生成级联反应和抗凋亡特性。我们的I期研究 在大鼠和小鼠中通过SF/HGF基因治疗证实了治疗性血管生成 外周缺血模型。我们将通过以下方式确认并扩展这项工作： 通过长期随访获得详细的剂量和时间过程信息 对于治疗益处以及对小鼠后肢的副作用 缺血模型我们还将研究SF/HGF基因治疗在以下方面的益处： 治疗衰老小鼠和糖尿病小鼠的外周缺血。的 将使用外周缺血的兔模型来评估 通过血流和后肢生理评估的SF/HGF基因治疗 灌注压和侧支血管发育的解剖学评估， 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VEGF治疗的有效性。这些目标 研究的目的是将SF/HGF基因治疗应用于临床实践。 拟定商业应用：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