Nicholas Johnson1, Kameron Bates2, Han Xie1, Lindsay Alfano3, John Vissing4, Tahseen Mozaffar5, Katherine Mathews6, Linda Lowes7, Matthew Wicklund8, Conrad Weihl9, Doris Leung10, Peter Kang11, Carla Zingariello12, Urvi Desai13, Erin DeSpain2, Mary St. Romain1, Jeffrey Statland14
1Virginia Commonwealth University, 2VCU, 3Nationwide Children'S Hospital, 4Rigshospitalet, 5University of California, Irvine, 6University of Iowa - Dept of Pediatrics, 7Nationwide Children's Hospital, 8University of Colorado, 9Washington University in St. Louis, 10Kennedy Krieger Institute, 11University of Minnesota Medical School, 12University of Florida, 13Dept of Neurology, CMC, 14University of Kansas Medical Center
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 disease caused by variants in the Fukutin-related protein (FKRP) gene, can lead to loss of ambulation, cardiomyopathy, and respiratory compromise. Advances in potentially 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.
Design/Methods:
A prospective 12-month observational study of clinically affected, genetically defined LGMD R9 participants was conducted at 11 international academic centers. COAs included the North Star Assessment for Limb Girdle Muscular Dystrophies (NSAD), the performance of upper limb 2.0 (PUL), and handheld dynamometry (HHD). Measurements were made at baseline, 6, 9, and 12 months. Participants were classified as ambulatory (A) or difficulty with ambulation (DA) based on a baseline 10-meter walk run threshold of ≥12 seconds. We present mean changes with standard deviations.
Results:
Eighty participants (55% women) completed 12 months of follow up. Most (65.2%) had homozygous FKRP variants. The mean age was 36.8 years, mean symptom onset was at 16.3 years, and mean duration was 10.4 years. 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% that did not differ based on gender, genetics, or ambulatory status. HHD was stable over 12 months, with changes ranging from -5.3% to 5.1%. Ninety-two participants are expected to complete follow up by November 2022.
Conclusions:
The NSAD could detect a modest but consistent loss in function at 12 months in LGMD R9; variability estimates collected will be important for future power calculations.
On behalf of GRASP-LGMD Consortium