Twelve-month functional change in Limb Gridle Muscular Dystrophy R9 / 2i

Topic:

Clinical Trials

Poster Number: 79

Author(s):

Nicholas Johnson, MD, MSCI, FAAN, Virginia Commonwealth University, Kameron Bates, MS, Virginia Commonwealth University, Han Xie, PhD, Virginia Commonwealth University, Lindsay Alfano, PT, DPT, PCS, Nationwide Children’s, John Vissing, MD, DMSci, Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Tahseen Mozaffar, MD, University of California Irvine, Katherine Mathews, MD, FAAN, University of Iowa, Linda Lowes, PT, PhD, Nationwide Children's Hospital, Matthew Wicklund, University of Colorado, Conrad Weihl, MD, PhD, Washington University School of Medicine, Doris Leung, MD, PhD, Kennedy Krieger Institution, Peter Kang, MD, Paul and Sheila Wellstone Muscular Dystrophy Center and Dept of Neurology, U of MN Medical School, Carla Zingariello, DO, University of Florida, Urvi Desai, MD, Neuroscience Institute, Atrium Health; Department of Neurology, Wake Forest U. School of Medicine, Erin DeSpain, MPA, Virginia Commonwealth University, Jessica St. Romain, Virginia Commonwealth University, Jeffrey Statland, MD, University 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 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