THERAPEUTIC ANGIOGENESIS BY SF/HGF GENE TRANSFER

治疗性血管生成，即使用生长因子来刺激动脉粥样硬化损伤区域的新血管形成，是治疗心血管疾病最有前途的新方法之一，心血管疾病是美国发病率和死亡率的主要原因。散点因子或肝细胞生长因子（SF/HGF）是一种多效性细胞因子，在体外和体内都具有显著的血管生成活性，可能是治疗用途的良好候选者。本项目拟评估SF/HGF基因转染在大鼠心肌和外周缺血模型中刺激血管生成的可行性。具体目的是：1)构建新的SF/HGF载体用于基因治疗实验；2)检测直接注射这些载体是否导致缺血组织中SF/HGF的表达；3)确定SF/HGF基因转移是否诱导体内血管生成。该研究的成功完成将导致更大动物的验证性实验和SF/HGF基因治疗的临床研究。拟议的商业应用：Angion Biomedica计划提交一份II期提案，以支持SF/HGF基因转移在大型动物模型中的研究以及在开始临床试验之前所需的毒理学研究。该公司希望与制药行业合作伙伴合作，进行SF/HGF基因转移的临床开发。Angion Biomedica公司与北岸大学医院签署了一项技术转让协议，其中包括一项正在申请的专利的独家许可，该专利涵盖了SF/HGF诱导血管生成的治疗用途。总体目标是开发一种安全可靠的治疗方法，包括心血管疾病患者的新生血管。

Therapeutic angiogenesis, i.e. use of growth factors to stimulate new blood vessel formation in areas of atherosclerotic damage, is one of the most promising new approaches to treatment of cardiovascular disease, the leading cause of morbidity and mortality in the US. Scatter factor or hepatocyte growth factor (SF/HGF) is a pleiotropic cytokine that has significant angiogenic activity in vitro and in vivo and may be a good candidate for therapeutic use. The project proposed will evaluate the feasibility of using SF/HGF gene transfer to stimulate angiogenesis in rat models of myocardial and peripheral ischemia. The specific aims are 1) to construct new SF/HGF vectors for use in gene therapy experiments; 2) to test whether direct injection of these vectors results in SF/HGF expression in ischemic tissue; and 3) to determine if SF/HGF gene transfer induces angiogenesis in vivo. Successful completion of the proposed studies will lead to confirmatory experiments in larger animals and clinical studies of SF/HGF gene therapy. PROPOSED COMMERCIAL APPLICATION: Angion Biomedica plans to submit a Phase II proposal to support studies of SF/HGF gene transfer in large animal models and the toxicology studies required before initiating clinical trails. The company expects to pursue clinical development of SF/HGF gene transfer in collaboration with a pharmaceutical industry partner. Angion Biomedica Corp. has signed a technology transfer agreement with North Shore University Hospital that includes an exclusive license for a pending patent covering therapeutic use of SF/HGF to induce angiogenesis. The overall goal is to develop a safe, reliable therapeutic approach for including neovascularization in patients with cardiovascular disease.