JOURNEY: A Multicenter, Longitudinal Natural History Study of Limb Girdle Muscular Dystrophy


Clinical Trials

Poster Number: T355


Herb Stevenson, MD, Sarepta Therapeutics, Inc, Linda Lowes, PT, PhD, Nationwide Children's Hospital, Roberto Vincent, MS, Sarepta Therapeutics, Inc., Wenhua Hu, PhD, Sarepta Therapeutics, Inc., Giacomo Pietro Comi, MD, PRESIDIO OSP MAGG POLICLINICO - PAD MONTEGGIA CLINICA NEUROLOGIA

Sarcoglycanopathies affect 1 in 178,000 people worldwide, accounting for 15%–20% of all limb girdle muscular dystrophy (LGMD) cases. However, data on the clinical characteristics and natural history of LGMD are limited. Here, we describe the clinical phenotype and natural disease course of LGMD sarcoglycanopathies (2E/R4, 2D/R3, and 2C/R5). JOURNEY (NCT04475926) is a global, multicenter, prospective, longitudinal study of LGMD2E/R4, 2D/R3, and 2C/R5 subtypes, with a planned enrollment of at least 90 participants. At enrollment, each subtype will be stratified by age (4–7, 8–16, and ≥17 years [y]) and ambulatory status. Primary endpoints are North Star Assessment for Dysferlinopathy (NSAD) score, performance of upper limb (PUL), pulmonary function tests, and other timed function tests. Exploratory assessments include electrocardiogram (ECG) and echocardiogram. Functional assessments will be conducted every 6 months over a 3-year period.
A total of 64 participants were enrolled as of January 2023 (2E/R4: n=28, 2D/R3: n=20, and 2C/R5: n=16; age 4–7y: n=7, 8–16y: n=19, and ≥17y: n=38). Half (32/64) are female and 36/64 (56.2%) are ambulatory (2E/R4: 14, 2D/R3: 15, and 2C/R5, 7). At baseline, 32.1% (2E/R4), 5.0% (2D/R3), and 37.5% (2C/R5) have cardiac disorders. Mean baseline NSAD and PUL scores by subtype and age (4–7y, 8–16y, ≥17y) are (NSAD) 2E/R4: 47.3, 35.9, 10.7; 2D/R3: 40.5, 30.6, 18.6; and 2C/R5: 43.0, 22.0, 2.1, respectively; and (PUL) 2E/R4: 37.3, 35.4, 20.4; 2D/R3: 27.0, 30.4, 25.7; and 2C/R5: 35.0, 27.8, 15.7, respectively. Baseline ECG is normal in 14/28 (50%), 11/20 (55%), and 10/16 (62.5%) of 2E/R4, 2D/R3, and 2C/R5 participants, respectively.
Understanding of the clinical characteristics and disease progression of LGMD may aid physicians with diagnosis and development of appropriate therapies.