• Linda P Lowes, Lindsay N Alfano, W David Arnold, Richard Shell, Thomas W Prior, Markus McColly, Kelly J Lehman, Kathleen Church, Douglas M Sproule, Sukumar Nagendran, Melissa Menier, Douglas E Feltner, Courtney Wells, John T Kissel, Samiah Al-Zaidy, and Jerry Mendell.
• Center for Gene Therapy at the Research Institute at Nationwide Children's Hospital, Columbus, Ohio; Department of Pediatrics, Ohio State University, Columbus, Ohio. Electronic address: linda.lowes@nationwidechildrens.org.
• Pediatr. Neurol. 2019 Sep 1; 98: 39-45.

BackgroundThis study characterizes motor function responses after early dosing of AVXS-101 (onasemnogene abeparvovec) in gene replacement therapy in infants with severe spinal muscular atrophy type 1 (SMA1).MethodsThis study is a follow-up analysis of 12 infants with SMA1 who received the proposed therapeutic dose of AVXS-101 in a Phase 1 open-label study (NCT02122952). Infants were grouped according to age at dosing and baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores: (1) early dosing/low motor, dosed age less than three months with scores <20 (n = 3), (2) late dosing, dosed at age three months or greater (n = 6), and (3) early dosing/high motor, dosed age less than three months with scores ≥20 (n = 3).ResultsEarly dosing/low motor group demonstrated a mean gain of 35.0 points from a mean baseline of 15.7, whereas the late dosing group had a mean gain of 23.3 from a mean baseline of 26.5. The early dosing/high motor group quickly reached a mean score of 60.3, near the scale maximum (64), from a mean baseline of 44.0. Despite a lower baseline motor score, the early dosing/low motor group achieved sitting unassisted earlier than the late dosing group (mean age: 17.0 vs 22.0 months). The early dosing/high motor group reached this milestone earliest (mean age: 9.4 months).ConclusionsThe rapid, significant motor improvements among infants with severe SMA1 treated with AVXS-101 at an early age highlight the importance of newborn screening and early treatment and demonstrate the therapeutic potential of AVXS-101 regardless of baseline motor function.Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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