308P Quantitative, clinical, and patient-reported outcome measures in patients with limb-girdle muscular dystrophy type R12: a 3-year follow-up study

Limb-girdle muscular dystrophy type R12 (LGMDR12) is a slowly progressive muscle disease characterized by weakness and atrophy of proximal limb muscles. As therapeutic options are developing, there is an unmet need to develop quantitative and reliable outcome measures. We investigated disease progression over 3 years in 18 patients with LGMDR12. Evaluations were done at baseline and after one and three years. Fat fraction of the lower back, thigh and calf from Dixon MRI will be measured using an AI model for automatic sequencing that is still under development. Muscle strength of the trunk, hip, and thigh was investigated with a Biodex dynamometer, handgrip strength with a handheld dynamometer, motor function with the motor function measure 32, and fatigue and lower back pain with questionnaires. We expect to present the 3-year fat fraction progression results from the AI model at the conference. With manual delineations at 1-year follow-up, we found increased muscle fat fraction in several back, thigh, and calf muscles (p<0.05). Handgrip strength and the total MFM32 score decreased only after 3 years (p<0.05). Stationary dynamometry, fatigue, and pain did not change significantly during the study. The present study demonstrates a slow disease progression in LGMDR12 affecting the paraspinal and leg muscles. We found progression of irreversible muscle damage in multiple muscles, while muscle strength tests could not detect changes in the same regions. This supports quantitative MRI as a surrogate outcome measure for natural history or clinical trials in LGMDR12.