Muscular Dystrophy Specialized Research Center

University Of Iowa, Iowa City IA

Investigators

Linked publications & trials

Abstract

OVERALL SUMMARY The overall goal of the University of Iowa Wellstone Muscular Dystrophy Specialized Research Center (MDSRC) is to perform research on muscular dystrophies (called dystroglycanopathies) that arise from absence or reduction in matriglycan on α-dystroglycan (α-DG). Dystroglycanopathies are a group of congenital/limb-girdle muscular dystrophies that lead to progressive skeletal muscle weakness and a decline in respiratory function. Project 1 (Campbell and Richerson) using mouse models of dystroglycanopathy will define the cellular and molecular mechanisms that underlie respiratory complications. Additional studies will determine the relationship between matriglycan length, laminin binding and α-DG receptor dysfunction in respiratory muscles; they will also determine the ability of potential therapies already in clinical trials to restore full-length matriglycan and normal respiratory function. Project 2 (Mathews and Saade) will define the natural histories of FKRP-related and non-FKRP-related dystroglycanopathies derived from an established, unique cohort of patients using established and evolving clinical measures, to optimize clinical care and facilitate clinical trial design, with a focus on those who might be excluded from current trials due to rare genotypes, young age or advanced disease. Extended follow up of non-FKRP genotypes will identify cohorts that share similar rates of motor progression who might be studied together in gene non-specific clinical trials. Novel potential biomarkers (electroretinograms and urine proteomics) identified in pilot work will be tested for relationship to motor manifestations. Core A (Campbell and Moore) is an administrative core that will coordinate the activities within and outside the Center to promote an interactive and collaborative research environment, and to engage patients in muscular dystrophy research. Core B (Moore), a Muscle-Tissue/Cell- Culture/Diagnostics Core, will support Projects 1 and 2, serve as a national tissue and cell-culture resource for research, provide specialized diagnostic testing for a wide range of muscular dystrophies, and maintain the infrastructure needed to evaluate muscle biopsies in support of clinical trials. Finally, Core C (Mathews and Campbell) will coordinate our Training initiatives. This Core will support basic science and clinical research training for medical students, postdoctoral trainees, graduate students, and undergraduate students who will conduct research in the Center and participate care of patients. Dr. Mathews and Saade will provide clinical research mentorship, Dr. Campbell will provide basic science training, and Dr. Moore will mentor neuromuscular pathology students. Core C will engage the wider MDSRC and neuromuscular disease communities by sponsoring annual symposia in coordination with the patient and family conference and by hosting pediatric muscular dystrophy conferences. The highly integrated cores and projects of this Center will accelerate the tempo of discovery in preclinical translational research and broadly impact the care of patients, from managing individuals to changing treatment paradigms affecting patient groups.