P.3.1 GNE myopathy functional activity scale (GNEM-FAS): Development of a disease-specific instrument for measuring function and independence

GNE myopathy or hereditary inclusion body myopathy (HIBM) is an autosomal recessive myopathy presenting with distal leg weakness in early adulthood. Progressive weakness results in greater dependence and disability over time. A disease-specific measurement of functional activity is needed to better understand the burden of illness, inform the design of clinical studies and optimize care. After clinical interview of patients, a 25-item questionnaire was developed to assess ability and independence in three domains: mobility, upper extremity (UE) use and self-care. Each item was rated from 0 to 4 with higher scores representing better function. Total scores range from 0 to 100; subscale scores range from 0 to 40 for Mobility, 0–32 for UE and 0–28 for Self-Care. The GNE Myopathy Functional Activity Scale (GNEM-FAS) was administered to 47 ambulatory subjects enrolled in a Phase 2 study of extended release sialic acid. Physical therapists completed the GNEM-FAS based on clinical observation and subject interview. Scores were compared to performance on volitional measures of strength and function, as well as scores on the Inclusion Body Myositis Functional Rating Scale (IBMFRS), a validated instrument for myositis. The mean GNEM-FAS total score was 69 out of 100 (23–94). Mobility subscores averaged 50%, UE, 81% and Self-Care, 82% of the maximum possible. Higher Mobility scores were associated with greater lower extremity strength ( r =0.83) and longer 6MWT distances ( r =0.83). A moderate association was seen between the UE domain scores and UE strength ( r =0.66). Self-care domain scores and the stair climb time were negatively related ( r =−0.68). There was a strong correlation between GNEM-FAS total scores and IBMFRS scores ( r =0.94). Mobility was limited more than UE or self-care function in this cohort of ambulatory subjects with GNE myopathy. Repeat administration in treated and untreated patients with varying degrees of severity is underway to further validate the instrument.