Category: Rare Genetic and Metabolic Diseases
Objective: To assess the impact of pegzilarginase therapy on gait kinematics in Arginase 1 Deficiency (ARG1-D) patients.
Background: High arginine levels in patients with ARG1-D are accompanied by a characteristic spastic diplegia with resultant gait deviations and functional immobility. A long-term open-label Phase 1/2 trial demonstrated that pegzilarginase-mediated lowering of arginine levels is accompanied by improvements in mobility assessments . To further evaluate these findings, we performed a blinded post hoc analysis of patient videos captured during this study.
Method: Compilation videos of pegzilarginase-treated patients performing the 6-min walk test and Gross Motor Function Measure at baseline, week 24, and week 48 were rated by 5 independent therapist-assessors for each patient (baseline to 24 weeks and 24 to 48 weeks) using a 7-point global impression of change Likert scale for 13 gait kinematics items (upper extremity/armswing, trunk position, pelvic tilt/rotation, hips, knees, ankles, weightshift/weight acceptance, stance/swing relationship, step/stride parameters, confidence, overall gait, stair ascension, and stair descension). Assessors were blinded to the time period of the videos. Hamstring and quadriceps muscle groups were assessed for spasticity at 24 and 48 weeks using the Modified Ashworth Scale (MAS).
Results: Patients were stratified according to baseline performance into high-functioning (HF) and low-functioning (LF) subgroups; 4 patients were HF (mean age, 8 y) and 3 were LF (mean age, 22 y). Through week 48, all 13 overground and ascension/descension items for all patients indicated a net improvement from baseline. Overall, 71% of improvement occurred from baseline to week 24 and 29% occurred from week 24 to week 48. Gait kinematics were either improved or clinically stabilized in 7/7 patients including those with longer duration of disease and more extensive functional mobility impairment at baseline (LF group). Total mean score improvement during the first 24 weeks was similar between groups (HF: 11.95; LF: 11.23). The largest improvement in both groups was in overall gait and stair ascension/descension measures. Spasticity was improved through 48 weeks in 6/7 patients and did not worsen in any patient.
Conclusion: Pegzilarginase treatment of ARG1-D resulted in improvements in gait, mobility, and spasticity.
References: Diaz GA et al. J Inherit Metab Dis. 2020 Dec 15 doi: 10.1002/jimd.12343.
To cite this abstract in AMA style:N. Foreman, G. Bubb, E. Bradford. Gait Improvement in Pegzilarginase-treated Patients With Arginase 1 Deficiency: A Blinded Kinematic Analysis [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/gait-improvement-in-pegzilarginase-treated-patients-with-arginase-1-deficiency-a-blinded-kinematic-analysis/. Accessed December 7, 2023.
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