Development of an Optimized Timed Up and Go (oTUG) for Measurement of Changes in Mobility Impairment in Facioscapulohumeral Muscular Dystrophy (FSHD) Clinical Trials

Objective: To develop a new clinical outcome assessment of mobility in FSHD. Background: FSHD is an autosomal dominant muscular dystrophy characterized by slowly progressive descending weakness and accumulation of physical disability. Patients consistently rank mobility issues including difficulty getting up from bed, standing up and walking as serious impairments. The Timed Up and Go (TUG) test is an objective assessment of mobility, but is insensitive to muscle weakness outside the legs. We hypothesized that a TUG that includes a supine-to-sit and sit-to-supine component could provide an optimized TUG (oTUG) to measure changes in mobility in FSHD clinical trials. Design/Methods: 22 FSHD patients were categorized by Ricci’s clinical severity scores (CSS range 0–5) into four groups (CSS 1–1.5: 6; CSS 2–2.5: 4; CSS 3–3.5:6 and CSS 4:6) and compared to 20 healthy controls. Each group performed the traditional TUG and oTUG on two visits one week apart. Results: Analysis of TUG by increasing CSS groups (1–4) respectively showed worsening mobility (in seconds, Mean and SD 8.7±2.1, 9±1.2, 10.3±5.4, 20±10.3) compared to healthy controls (7.1±1.3). The oTUG also showed progressively worse mobility (Mean and SD 13.6±4.6, 15.2± 2.2, 16.8± 7.9, 29.5± 11.1) compared to healthy controls (10±1.9). The supine-to-sit assessment also showed clear worsening by CSS groups 1–4 (Mean and SD 2.4±1.1, 2.7± 0.8, 3.1±1.7, 5.1± 1.7) compared to healthy controls (1.7±0.4). The test-retest assessment shows strong reliability for both the traditional TUG and the oTUG. Conclusions: Both TUG and oTUG show clear differences in FSHD from healthy controls. We have developed a modified TUG that is optimized for FSHD, and has the potential to show better responsiveness to therapeutic intervention in FSHD clinical trials by incorporating mobility of the trunk. Disclosure: Dr. Chan has nothing to disclose. Dr. Hatch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Research project money from Fulcrum Therapeutics. Dr. Kurillo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bioniks and Applied BioMechanics, Inc.. Dr. Han has nothing to disclose. Dr. Cadavid has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Fulcrum Therapeutics. Dr. Cadavid has received research support from Fulcrum Therapeutics.