National Center for Canine Models of Duchenne Muscular Dystrophy (NCDMD)

国家杜氏肌营养不良犬模型中心 (NCDMD)

• 批准号: 7696322
• 负责人: Joe N. Kornegay
• 金额: $ 99.16万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7696322
• 关键词: Address; Affect; Animal Diseases; Animal Model; Animals; Breeding; Canis familiaris; Caring; Charge; Clinical; Clinical Research; Clinical Trials; Collaborations; Condition; Country; Data; Development; Disease; Duchenne muscular dystrophy; Dystrophin; Ensure; Fees; Fees and Charges; Felis catus; Goals; Grant; Health Services Research; Histology; Human; Image; Intellectual Property; Investigational Drugs; Investigational New Drug Application; Lead; Link; Modeling; Molecular; Mus; Muscular Dystrophies; Myocardium; Newborn Infant; Operative Surgical Procedures; Pathogenesis; Phase; Physiology; Policies; Positioning Attribute; Preclinical Testing; Procedures; Process; Proteins; Quality Control; Recommendation; Research; Research Infrastructure; Research Personnel; Research Project Grants; Rodent Model; Services; Skeletal system; Standards of Weights and Measures; Structure; Testing; Therapeutic; Therapeutic Agents; Translational Research; Translations; Treatment outcome; United States Food and Drug Administration; Validation; Work; base; career; cost; day; gene therapy; human male; mdx mouse; novel therapeutics; preclinical study; programs; response

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder affecting approximately 1 of 3,500 newborn human males in which absence of the protein dystrophin causes progressive degeneration of skeletal and cardiac muscle. Currently no treatment halts or reverses progression of DMD. Although cellular and gene therapies are promising, key questions must first be addressed in relevant animal models. Spontaneous forms of X-linked muscular dystrophy due to dystrophin deficiency have been identified in mice, multiple dog breeds, and cats. Unlike the dystrophin-deficient mdx mouse, which remains relatively normal clinically, affected dogs develop progressive, fatal disease strikingly similar to the human condition. Accordingly, studies in the canine dystrophin deficient models, such as golden retriever muscular dystrophy (GRMD), are more likely than those in mdx mice to predict pathogenesis and outcome of treatment in DMD. Using FDA recommendations as a guiding principle, we have formulated a research initiative titled the National Center for Canine Models of Duchenne Muscular Dystrophy (NCDMD). The overarching goal of the NCDMD is to develop and sustain dog models of DMD and expand country-wide collaborations with investigators pioneering translational research focused on the treatment of DMD. UNC is uniquely positioned to carry out this initiative having successfully developed a similar structure for the UNC hemophilic canine model. The emerging need for access to the GRMD and other DMD canine models is becoming imminent. Five therapeutic approaches detailed later in this summary are representative of the various approaches that have shown promise in the mdx mouse and are now poised for further studies in canine models before entering clinical studies. Without the proposed NCDMD, it will be virtually impossible to meet the increasing demand to utilize GRMD and other canine models of DMD in critical preclinical studies required for human clinical trials. The NCDMD will also provide high quality facilities and services in compliance with GLP standards to support pre-IND applications.

Duchenne肌肉营养不良症（DMD）是一种X连锁隐性疾病，影响了3,500个中的1个 新生的人类雄性缺乏蛋白质肌营养不良蛋白会导致进行性变性 骨骼和心肌。目前尚未停止或逆转DMD的进展。虽然细胞 基因疗法是有希望的，首先必须在相关动物模型中解决关键问题。 由于肌营养不良蛋白缺乏引起的X连锁肌营养不良的自发形式已在 小鼠，多个狗品种和猫。与肌营养不良蛋白缺陷的MDX小鼠不同，该小鼠保持相对 正常临床上，受影响的狗会发展为进行性致命疾病，与人类状况极为相似。 因此，在犬肌营养不良蛋白缺乏模型中的研究，例如金毛肌营养不良症 （GRMD）比MDX小鼠中的那些更有可能预测DMD治疗的发病机理和结果。 使用FDA建议作为指导原则，我们制定了一项名为The的研究计划 杜兴肌营养不良症（NCDMD）的国家犬犬模型中心。总体目标 NCDMD将开发和维持DMD的狗模型，并扩大全国范围内的合作 研究人员开创性转化研究的重点是DMD的治疗。 UNC是独特的位置 为了成功地为UNC血友犬开发了类似的结构，以执行这项计划 模型。访问GRMD和其他DMD犬模型的新兴需求即将变得越来越大。 本摘要后面详细介绍的五种治疗方法代表了各种方法 已经在MDX鼠标中显示了希望，现在已经准备好在犬模型之前进行进一步研究 进入临床研究。没有提议的NCDMD，几乎不可能达到增加的 在人类所需的批判性临床前研究中，需要利用GRMD和其他DMD犬模型 临床试验。 NCDMD还将为GLP提供高质量的设施和服务 支持预先申请的标准。