Clinical Trial Readiness in Limb Girdle Muscular Dystrophy R1 (LGMDR1): A GRASP Consortium Study

\ua9 2025 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.Objective: Identifying functional measures that are both valid and reliable in the limb girdle muscular dystrophy (LGMD) population is critical for quantifying the level of functional impairment related to disease progression in order to establish clinical trial readiness in the context of anticipated therapeutic trials. Methods: Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 subjects with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each subject completed a battery of clinical outcome assessments (COA), including the North Star Assessment for Limb Girdle-Type Dystrophies (NSAD), 10-m walk/run, and Performance of the Upper Limb (PUL), in addition to several patient-reported outcome measures (PROM). Results: In this baseline cross-sectional analysis, significant correlations were found between COAs and PROMs, with significant differences in the performance of assessments based on subjects\u27 ambulatory status and genetic variant classification. Interpretation: The study has determined that the NSAD and other assessments are valid and reliable measures for quantifying the level of disease impairment in individuals with LGMDR1

Prospective observational study of FKRP-related limb-girdle muscular dystrophy R9: A GRASP consortium study

\ua9 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. Objective: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP) natural history study. Methods: Enrolled patients completed a battery of COA on two consecutive days, including the North Star Assessment for limb girdle-type dystrophies (NSAD), the 100-m timed test (100 m), and the Performance of Upper Limb 2.0 (PUL). Results: A total of 101 patients with FKRP-related LGMDR9 completed COA evaluations. All functional COA were highly and significantly correlated even across constructs, except for the 9-hole peg test. Similarly, all tests demonstrated excellent test–retest reliability across 2-day visits. The NSAD and PUL demonstrate robust psychometrics with good targeting, ordered response thresholds, fit and stability, and limited dependency of items across the scales. Conclusions: This study has determined the suitability of several functional COA, cross-sectionally, in LGMDR9 to inform future trial design and clinical care