Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy.
Pediatr Neurol
; 98: 39-45, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31277975
ABSTRACT
BACKGROUND:
This 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).METHODS:
This 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).RESULTS:
Early 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).CONCLUSIONS:
The 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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
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Atrofias Musculares Espinais da Infância
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Avaliação de Resultados em Cuidados de Saúde
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Proteínas do Complexo SMN
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Transtornos Motores
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article