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.
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