Maintenance of Animal Models of Human Hemophilia and VWD

人类血友病和 VWD 动物模型的维持

基本信息

批准号：
8286377
负责人：
Timothy Charles Nichols
金额：
$ 72.29万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-15 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8286377
关键词：
Accreditation Acute Address Animal Experimentation Animal Model Animals Antibodies Antigens Applications Grants Area Award Benchmarking Biological Assay Blood Blood Banks Blood Platelets Blood coagulation Blood donor Breeding Busulfan Canis familiaris Central Vein Cesarean section Chronic Clinical Coagulation Process Collaborations Communities Cyclophosphamide Cyclosporine Detection Disease Ensure Environment Erythrocytes Event Fresh Frozen Plasmas Functional disorder Funding Funding Agency Gene Transfer Germ Lines Grant Health Services Research Hemophilia A Hemophilia B Hemorrhage Hepatic artery Hereditary Disease Housing Human Human Resources IACUC Immune response Inherited Institution Intramuscular Investigation Isolated limb perfusion Laboratory Research Lymphocyte Maintenance Manuscripts Messenger RNA Modeling Monitor North Carolina Operative Surgical Procedures Peer Review Performance Pharmaceutical Preparations Portal vein structure Preclinical Testing Procedures Production Protocols documentation Publications Publishing Peer Reviews Quality Control Regulation Reporting Research Research Personnel Research Project Grants Resources Route Safety Testing Therapeutic Therapeutic Agents Thrombosis Training Translating Trauma United States National Institutes of Health Universities Walking Whole Blood Work abstracting animal care blood product clinical practice cost cost effective design editorial enzyme replacement therapy experience gene therapy immunoregulation inhibitor/antagonist meetings novel operation quality assurance repaired research study von Willebrand Disease von Willebrand Factor

项目摘要

The purpose of this resource grant is to function as a core to maintain and create dogs with hemophilia A, hemophilia B, and von Willebrand disease (WVD) for collaborations with other investigators. Our objectives are: 1) To maintain a breeding colony of well-characterized dogs with genetically-determined bleeding disorders at the Francis Owen Blood Research Laboratory (FOBRL), University of North Carolina, Chapel Hill; 2) To produce purpose-bred, affordable research animals with these bleeding disorders in a cost effective manner; and 3) To provide specialized support services for research projects using these dogs including canine blood banking and coagulation analyses. These dogs, identified by Dr. Kenneth M. Brinkhous, model human hemophilias and VWD and have been maintained for >50 years at UNC largely through NIH support. Research using the FOBRL dogs has more than doubled during the past 20 years and has led to discoveries that have revolutionized the treatment of inherited and acquired bleeding and thrombotic disorders. Many therapeutic agents were developed and tested in these dogs and successfully translated into clinical therapeutics. Thus many advisory boards recommend these dogs as essential for preclinical testing of new treatments for the hemophilias, VWD, and hemorrhage. Major accomplishments during the past 5 years include 24 peer-reviewed publications, over 36 abstract presentations, and obtaining funding separate from but leveraged by this grant that built new, dedicated hemophilia and VWD dog housing. A highly trained staff at the FOBRL has several years of experience in maintaining these special dogs with a dedicated canine blood bank, developing canine coagulation assays, conducting investigations, and collaborating successfully with investigators worldwide. Current research addresses several unmet national needs that include testing new treatments for bleeding, developing a new strain of hemophilia A dogs with inhibitors, and determining the acute and chronic sequelae of gene therapy on genetic diseases. This grant is the only support for maintenance of this colony. Without this grant, new research using these valuable bleeder dogs would be very difficult and expensive to initiate and the survival of this colony would be jeopardized. The cost of establishing a colony at each investigator's institution is prohibitive. This Resource Grant is essential to ensure the survival of the colony in an established, successful environment.

该资源赠款的目的是作为核心，以与其他研究人员的合作维持和创建狗A，血友病B和Von Willebrand疾病（WVD）。我们的目标是：1）在北卡罗来纳大学北卡罗来纳大学的弗朗西斯·欧文血液研究实验室（FOBRL），维持良好特征的狗的繁殖菌落，并在遗传确定的出血性疾病中保持遗传性出血疾病； 2）以具有成本效益的方式生产具有这些出血疾病的目的，负担得起的研究动物； 3）使用这些狗（包括犬血库和凝结分析）提供专门的研究项目。这些狗是由肯尼斯·M·布林克斯（Kenneth M. Brinkhous）博士确定的，建模了人类血友病和VWD，并在UNC上维持了50年，主要是通过NIH支持。在过去的20年中，使用FOBRL犬的研究增加了一倍以上，并导致发现彻底改变了对遗传和获得的出血和血栓性疾病的治疗。在这些狗中开发和测试了许多治疗剂，并成功地转化为临床治疗剂。因此，许多咨询委员会建议这些狗对于对血友病，VWD和出血的新疗法进行临床前测试至关重要。在过去的5年中，主要成就包括24个经过同行评审的出版物，超过36个抽象演讲，并获得了与这笔赠款分开的资金，该资助建造了新的，专门的血友病和VWD狗住房。 FOBRL的训练有素的员工在与专用的犬血库维护这些特殊狗方面拥有多年的经验，开发了犬凝结测定，进行调查以及与全球调查人员成功合作。当前的研究解决了几种未满足的国家需求，包括测试用于出血的新疗法，开发具有抑制剂的新型血友病A狗，并确定基因治疗对遗传疾病的急性和慢性后遗症。这笔赠款是维持这个殖民地的唯一支持。没有这笔赠款，使用这些有价值的流血犬的新研究将非常困难和昂贵，并且该殖民地的生存将受到危害。在每个调查员的机构中建立殖民地的成本是高度的。这项资源赠款对于确保殖民地在建立成功的环境中的生存至关重要。