Objective: To determine progression in limb girdle muscular dystrophy R9 (LGMD R9) measured by functional clinical outcome assessments (COAs).
Background: LGMD R9, an autosomal recessive form of LGMD due to missense mutations in the Fukutin-related protein (FKRP) gene, can lead to loss of ambulation, cardiomyopathy, and respiratory compromise. Advances in disease modifying therapies raise the possibility of disease altering clinical trials. A barrier to clinical trials is an incomplete understanding of LGMD R9 disease progression.
Methods: Prospective 12-month observational study of clinically affected and genetically defined LGMD R9 participants seen at 11 international academic centers. COAs included the North Star Assessment for Limb Girdle Muscular Dystrophies (NSAD), the performance upper limb 2.0 (PUL), and handheld dynamometry (HHD, 6 bilateral upper extremity muscles). Measurements were made at baseline, 6, 9, 12, and 24 months (12 months data presented here). Participants were split into ambulators (A) and difficulty with ambulation (DA) based on baseline 10-meter walk run ≥ 12 seconds. We present mean changes with standard deviation.
Results: Eighty participants have completed 12 months of follow up. The cohort was comprised of 56% women, mean age 36.6 years, mean symptom onset at 16.3 years, mean duration 10.4 years, and mostly homozygous (65.2%) mutations. The NSAD showed an average loss of function of -1.1 points (SD 3.2) or 5.3%, which was larger for men (8.8%) . The PUL was stable with a mean loss of -0.73 points (SD 2.5) or 1.8%, which showed no difference based on gender, genetics, or ambulatory status. HHD was stable over 12 months, with a range of change from -5.3% to 5.1%.
Conclusion: The NSAD could detect a modest consistent loss in function at 12 months in LGMD R9, with variability estimates important for future power calculations.
Funding: ML Bio Solutions