TY - JOUR
T1 - Natural history of limb girdle muscular dystrophy R1 (LGMDR1)
T2 - a GRASP consortium study
AU - GRASP-LGMD Consortium
AU - Hunn, Stephanie M.
AU - Findlay, Andrew R.
AU - Alfano, Lindsay N.
AU - Jones, Aileen
AU - Butler, Amanda
AU - Lowes, Linda P.
AU - Iammarino, Megan A.
AU - Reash, Natalie F.
AU - Pietruszewski, Lindsay
AU - Sasidharan, Sandhya
AU - Currence, Melissa
AU - Statland, Jeffrey M.
AU - Strahler, Talia
AU - Will, Robert
AU - Wicklund, Matthew
AU - Dixon, Stacy
AU - Augsburger, Renee
AU - Mozaffar, Tahseen
AU - Laubscher, Katie M.
AU - Mockler, Shelley R.H.
AU - Mathews, Katherine D.
AU - Stinson, Nikia
AU - Leung, Doris G.
AU - Stark, Molly M.
AU - Horton, Rebecca A.
AU - Kang, Peter B.
AU - James, Meredith K.
AU - Clause, Amanda
AU - Weihl, Conrad C.
AU - Johnson, Nicholas E.
N1 - Publisher Copyright:
© 2026 The Authors
PY - 2026/6
Y1 - 2026/6
N2 - Identifying clinical outcome assessments (COAs) that are able to detect change in functional abilities over time in the limb girdle muscular dystrophy (LGMD) population is critical for managing disease progression in addition to determining drug efficacy in the context of anticipated therapeutic trials. Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 participants with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each participant completed a battery of COAs, including the North Star Assessment for Limb Girdle-Type Muscular Dystrophies (NSAD), 100-meter timed test (100 m), Performance of the Upper Limb (PUL), and 4-Stair Climb (4SC) in addition to several patient-reported outcome measures (PROM) across three time points in this year-long study. Participants with LGMDR1 demonstrate significant decline in the 100 m, NSAD, PUL, and 4SC over a 12-month time period. The rate of decline was greater in those considered to be higher functioning (10-meter time <12 s) while genetic variant types did not appear to significantly influence the rate of decline in our cohort. A combination of COAs is determined to be the best approach at measuring functional change over time in patients with LGMDR1.
AB - Identifying clinical outcome assessments (COAs) that are able to detect change in functional abilities over time in the limb girdle muscular dystrophy (LGMD) population is critical for managing disease progression in addition to determining drug efficacy in the context of anticipated therapeutic trials. Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 participants with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each participant completed a battery of COAs, including the North Star Assessment for Limb Girdle-Type Muscular Dystrophies (NSAD), 100-meter timed test (100 m), Performance of the Upper Limb (PUL), and 4-Stair Climb (4SC) in addition to several patient-reported outcome measures (PROM) across three time points in this year-long study. Participants with LGMDR1 demonstrate significant decline in the 100 m, NSAD, PUL, and 4SC over a 12-month time period. The rate of decline was greater in those considered to be higher functioning (10-meter time <12 s) while genetic variant types did not appear to significantly influence the rate of decline in our cohort. A combination of COAs is determined to be the best approach at measuring functional change over time in patients with LGMDR1.
KW - Calpainopathy
KW - Limb girdle muscular dystrophy
KW - Natural history
KW - Outcome measures
UR - https://www.scopus.com/pages/publications/105035115648
UR - https://www.scopus.com/pages/publications/105035115648#tab=citedBy
U2 - 10.1016/j.nmd.2026.106416
DO - 10.1016/j.nmd.2026.106416
M3 - Article
C2 - 41962316
AN - SCOPUS:105035115648
SN - 0960-8966
VL - 63
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
M1 - 106416
ER -