Characterization of Strength and Function in Ambulatory Adults With GNE Myopathy

Abstract

Objective:To characterize the pattern and extent of muscle weakness and impact on physical functioning in adults with GNEM.Methods:Strength and function were assessed in GNEM subjects (n = 47) using hand-held dynamometry, manual muscle testing, upper and lower extremity functional capacity tests, and the GNEM-Functional Activity Scale (GNEM-FAS).Results:Profound upper and lower muscle weakness was measured using hand-held dynamometry in a characteristic pattern, previously described. Functional tests and clinician-reported outcomes demonstrated the consequence of muscle weakness on physical functioning.Conclusions:The characteristic pattern of upper and lower muscle weakness associated with GNEM and the resulting functional limitations can be reliably measured using these clinical outcome assessments of muscle strength and function.

A phase 3 randomized study evaluating sialic acid extended-release for GNE myopathy

“…One of the most promising highlights from the clinical trials investigating the efficacy and safety of Ace-ER was the development of the GNEM-FAS, another validated tool that will set the stage for future clinical studies in the GNE myopathy population. 13,14…”

“…The endpoints evaluated in UX001-CL301 were determined by analysis of phase 2 data (UX001-CL201; NCT01517880) assessing outcome measures capable of characterizing the pattern and extent of muscle weakness associated with GNE myopathy and functional limitations resulting from this weakness. 13 All efficacy assessments were conducted on site at screening or baseline and every 8 weeks following baseline.…”

“…For key secondary endpoints, the following change from baseline to week 48 was evaluated for both treatment groups: lower extremity (LE) muscle strength composite (LEC) score, muscle strength in knee extensors, and physical functioning as measured using the GNE myopathy–Functional Activity Scale (GNEM-FAS) mobility domain score. 13,14 The GNEM-FAS is a validated instrument with qualitative and quantitative measures designed to assess functional impairment in GNE myopathy including mobility, UE function, and self-care; higher GNEM-FAS scores indicate a lower level of impairment. LEC was calculated as the sum of the following muscle groups using HHD: hip abductors and adductors, hip flexors and extensors, and knee flexors.…”

“…Knee extensor muscle strength was also measured by HHD. The following additional secondary endpoints were also evaluated for both treatment groups at week 48: physical functioning as measured using the GNEM-FAS UE domain score 13,14 ; UE function as measured by a timed weighted arm lift test 15 ; LE function as measured by a timed Sit-to-Stand Test 15,16 ; LE function as measured by distance walked in the 6MWT 17 ; and the quality of life questionnaire for neuromuscular disease. 18 Blood samples were collected at baseline and prior to drug administration every 8 weeks thereafter to assess change in free serum SA using liquid chromatography atmospheric pressure ionization mass spectrometry (response range 0.0400–20.0 μg/mL) performed by Intertek Pharmaceutical Services (San Diego, CA).…”

Limitations of 6‐minute walk test reference values for spinal muscular atrophy

“…It is important to point out that three healthy normative reference equations, commonly used in various neuromuscular studies, fail to meet our inclusion criteria. Currently, the published norms for the 6MWT most widely used are the Geiger norms for pediatric populations, and the Enright or Gibbons norms for adult populations.…”