BONE REGENERATION BY SF/HGF GENE ACTIVATED MATRIX

使用生长因子促进骨愈合的前景尚未实现。使用编码生长因子基因的病毒载体进行基因治疗可能具有临床实用价值，因为它延长了对感兴趣细胞因子的暴露时间。我们将评估SF/HGF，一种多效性生长因子，作为一种蛋白质和在基因激活的基质中的活性，在股骨缺损性动物模型中。在特定的目的一，我们将研究重组人生长因子/肝细胞生长因子对血管生成和愈合的影响。在特定目的2中，我们将在相同的动物模型上研究SF/HGF基因激活基质的治疗效果。这些研究的结果将为第二阶段项目开发临床应用的SF/HGF基因疗法提供基础。建议的商业应用：建议的项目将产生关于一种重要的细胞因子-分散因子肝细胞生长因子(SF/HGF)促进骨再生的作用的新信息。愈合不充分是骨质疏松性和不可愈合性骨折患者发病率和生活质量下降的一个重要原因。在美国，每年治疗这些患者的总成本超过90亿美元。如果研究成功，Angion Biomedica将实施第二阶段计划，为SF/HGF基因疗法的临床开发提供骨再生的基础。

The promise of using growth factors to improve bone healing has not yet been realized. Gene therapy with viral vectors coding for growth factor genes may have clinical utility because it prolongs exposure to the cytokine of interest. We will evaluate the activity of SF/HGF, a pleiotropic growth factor, as a protein and in a gene activated matrix in an animal model of femoral gap defect. In Specific Aim I we will examine the effects of rhSF/HGF on angiogenesis and healing. In Specific Aim 2 we will study the effects of treating with SF/HGF gene activated matrix in the same animal model. The results from these studies will provide the basis for a Phase II project to develop gene therapy with SF/HGF for clinical applications. PROPOSED COMMERCIAL APPLICATIONS: The project proposed will generate new information on the role of an important cytokine, scatter factor hepatocyte growth factor (SF/HGF) for promoting regeneration of bone. Inadequate healing is a significant cause of morbidity and compromised quality of life in patients with osteoporotic and non-healing bone fractures. The collective costs of treating these patients is more than $9 billion per annum in flee U.S. If the studies are successful, Angion Biomedica will pursue a Phase II program to provide the basis for clinical development of SF/HGF gene therapy for bone regeneration.