Gene Therapy for Hemophilia A

描述（由申请人提供）：广泛努力开发一种安全且 血友病A基因治疗有效方法尚未取得成功。在 本项目申请人将测试一种有前途的体外方法， 第八因子利用最近发现的一种叫做血液的细胞群 长出内皮细胞或BOEC。首席研究员已经证明， 工程BOEC可以安全地用于提供持续的，治疗水平的 血友病A小鼠模型中的FVIII。该项目的具体目标是 证明工程化的BOEC可用于实现治疗水平的 A型血友病犬的犬凝血因子VIII。在这项研究中，BOEC 将从两只血友病A犬中获得，用fVIII转染并输注 变成同样的动物。凝血因子VIII水平将在 时间如果检测到治疗水平，角质层出血时间也将减少。 测定如果如预期的那样，在本研究中获得了肯定的结果， 申请人打算继续进行完整的临床前开发计划， BOEC技术，并为血友病A适应症提交IND。 拟定商业应用： BOEC代表了基因治疗和其他医学应用的新平台技术。 这项研究和后续研究的成功可能会导致BOEC技术的最终批准 作为A型血友病和其他适应症的优选疗法。

DESCRIPTION (provided by applicant): Extensive efforts to develop a safe and effective method of gene therapy for hemophilia A have not met with success. In this project the applicant will test a promising ex vivo approach to delivering factor VIII using a recently identified population of cells called blood outgrowth endothelial cells or BOEC. The principal investigator has shown that engineered BOEC may safely be used to provide sustained, therapeutic Levels of fVIII in a mouse model of hemophilia A. The Specific Aim of this project is to demonstrate that engineered BOEC can be used to achieve therapeutic levels of canine coagulation factor VIII in the hemophilia A dog. In this study, BOEC will be obtained from two hemophilia A dogs, transfected with fVIII and infused into the same animals. Coagulation factor VIII levels will be assayed over time. If therapeutic levels are detected, cuticle bleed times will also be determined. If, as expected, affirmative results are obtained in this study, the applicant intends to pursue a full preclinical development plan for the BOEC technology and to file an IND for the hemophilia A indication. PROPOSED COMMERCIAL APPLICATION: BOEC represent a novel platform technology for gene therapy and other medical applications. Success in this and subsequent studies could lead to the ultimate approval of BOEC technology as a preferred therapy for hemophila A and other indications.