Investigates the cellular and molecular mechanisms that underly dystroglycanopathies using state-of-the-art biochemical, cell biological and glycobiological approaches, recombinant enzymes, and studies in a dystroglycanopathy mouse model. Mechanistic insights into the dystroglycanopathies will provide a rationale for the design of novel diagnostic and therapeutic strategies, as well as approaches to monitoring therapeutic engagement and efficacy.
Characterizes the natural history of the dystroglycanopathies using established and evolving clinical measures to optimize clinical care as well as inform and enhance clinical trial design. Project 2 will refine the natural history of FKRP-related dystroglycanopathy derived from an established, unique cohort of patients and extend follow up of non-FKRP, dystroglycanopathy genotypes to identify cohorts that share similar rates of motor progression who might be studied together in gene non-specific clinical trials. Candidate proteomic biomarkers in blood or urine for the full spectrum of dystroglycanopathy genotypes will be validated and related to disease status.