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

Area of Science:

• Neurology
• Genetics
• Clinical Trials

Background:

• Limb-girdle muscular dystrophy R9 (LGMDR9), caused by FKRP gene variants, results in progressive muscle weakness and motor function loss.
• Standardized clinical outcome assessments (COA) are crucial for effective disease management and clinical trial design in LGMDR9.
• Identifying appropriate COA helps define endpoint selection and enrollment criteria for therapeutic studies.

Purpose of the Study:

• To evaluate the cross-sectional validity and reliability of functional COA in patients with FKRP-related LGMDR9.
• To inform the selection of the most suitable COA for capturing disease presentation and progression in LGMDR9.

Main Methods:

• 101 patients with FKRP-related LGMDR9 were enrolled in the GRASP natural history study.
• Participants completed a battery of COA, including the North Star Assessment for limb girdle-type dystrophies (NSAD), 100-m timed test, and Performance of Upper Limb 2.0 (PUL), on two consecutive days.

Main Results:

• All tested functional COA demonstrated high and significant correlations, with the exception of the 9-hole peg test.
• Excellent test-retest reliability was observed for all COA across 2-day visits.
• The NSAD and PUL exhibited robust psychometric properties, including good targeting, ordered response thresholds, and stability.

Conclusions:

• The study confirmed the suitability of several functional COA for cross-sectional evaluation in LGMDR9.
• These findings will aid in optimizing future clinical trial design and improving patient care for LGMDR9.