National Center for Canine Models Muscular Dystrophy (NCDMD)

国家肌营养不良犬模型中心 (NCDMD)

• 批准号: 7912827
• 负责人: Joe N. Kornegay
• 金额: $ 9.5万
• 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 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7912827
• 关键词: National; Center; Canine; Models; Muscular

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：Duchenne肌肉营养不良症（DMD）是一种X连锁的隐性疾病，影响了3500名新生的男性中约1个，其中缺乏蛋白质肌营养不良蛋白会导致骨骼肌和心脏肌肉的进行性退化。目前尚未停止或逆转DMD的进展。尽管细胞和基因疗法是有希望的，但必须首先在相关动物模型中解决关键问题。在小鼠，多种狗品种和猫中已经发现了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。与肌营养不良的MDX小鼠在临床上保持相对正常的MDX小鼠不同，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，例如黄金猎犬肌肉营养不良（GRMD），比MDX小鼠中的研究更有可能预测DMD治疗的发病机理和治疗结果。我们使用FDA建议作为指导原则，我们制定了一项研究计划，名为《杜钦肌营养不良症犬犬模型中心》（NCDMD）。 NCDMD的总体目标是开发和维持DMD的狗模型，并扩大与调查员开创性转化研究的全国合作，重点是DMD处理。 UNC在成功开发了UNC亲血性犬模型的类似结构方面是独特的，可以执行这项计划。访问GRMD和其他DMD犬模型的新兴需求即将变得越来越大。本摘要稍后详细介绍的五种治疗方法代表了在MDX小鼠中表现出希望的各种方法，现在已经准备好在进入临床研究之前在犬模型中进行进一步研究。没有拟议的NCDMD，在人类临床试验所需的重要临床前研究中，几乎不可能满足使用GRMD和其他DMD的其他DMD犬模型的需求。 NCDMD还将根据GLP标准提供高质量的设施和服务，以支持预先申请。