Trial Readiness and Endpoint Assessment in LGMD R1

Limb girdle muscular dystrophies (LGMD) are a group of over 30 heterogenous genetic disorders which have in common a pattern of weakness affecting proximal muscles of the shoulders and hips. LGMD type R1 (LGMDR1; also LGMD2A) is due to loss of function of the muscle structural gene calpain 3 (CAPN3) and causes progressive weakness and muscle wasting, which can lead to loss of ambulation or the ability to maintain a job. LGMDR1 is one of the most common LGMDs in the United States and has no FDA approved therapies but is amenable to gene replacement strategies, regenerative medicine approaches, or myostatin based approaches. There have been rapid advances in gene delivery therapies for Duchenne Muscular Dystrophy and for LGMDR4 that have set the stage for targeted therapeutic development for all LGMDs, and LGMDR1 in particular is at a crossroads: the pace of therapeutic development has outstripped the efforts at clinical trial preparedness.

There is a need for a more rigorous natural history study to assist in the design of clinical trials; in particular, identifying biomarkers for early phase development and clinical outcome assessments (COAs) for drug approval studies.

This study will enroll 100 subjects across participating sites in the GRASP-LGMD Research Consortium. No treatment will be administered as part of this study. A subset of 80 patients will undergo MR scans at selected imaging sites. Study visits will occur at Baseline Day 1, Baseline Day 2, Month 12, and Month 24.