Gene replacement therapy for spinal muscular atrophy: safety and preliminary efficacy in a Brazilian cohort.

Autor: Mendonça RH; Department of Neurology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil. rodrigo.holanda@hc.fm.usp.br.; Hospital Samaritano Higienópolis, São Paulo, Brazil. rodrigo.holanda@hc.fm.usp.br., Ortega AB; Hospital Pequeno Príncipe, Curitiba, Brazil., Matsui C Jr; Department of Neurology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.; Hospital Samaritano Higienópolis, São Paulo, Brazil., van der Linden V; Hospital Maria Lucinda, Recife, Brazil., Kerstenetzky M; Hospital Maria Lucinda, Recife, Brazil., Grossklauss LF; Hospital Infantil Sabará, São Paulo, Brazil., Silveira-Lucas EL; Hospital Moinhos do Vento, Porto Alegre, Brazil., Polido GJ; Department of Neurology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil., Zanoteli E; Department of Neurology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Gene therapy [Gene Ther] 2024 Jul; Vol. 31 (7-8), pp. 391-399. Date of Electronic Publication: 2024 Jun 05.
DOI: 10.1038/s41434-024-00456-y
Abstrakt: Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness, ventilatory failure, and reduced survival. Onasemnogene abeparvovec is the first gene replacement therapy (GT) approved to treat this condition. An observational retrospective study was conducted to assess adverse events and efficacy of GT in SMA patients. Forty-one patients with SMA (58.5% females and 80.1% SMA type 1) were included. The mean age at GT dosing was 18 (±6.4) months. Thirty-six patients (87.8%) were under previous treatment with nusinersen, and 10 (24.4%) continued nusinersen after GT. Mean CHOP-INTEND increased 13 points after 6 months and this finding did not differ between groups according to nusinersen maintenance after GT (p = 0.949). Among SMA type 1 patients, 14 (46.6%) reached the ability to sit alone. Liver transaminases elevation at least two times higher than the upper limit of normal value occurred in 29 (70.7%) patients. Thrombocytopenia occurred in 13 (31.7%) patients, and one presented thrombotic microangiopathy. Older age (>2 years) was associated with more prolonged use of corticosteroids (p = 0.021). GT is effective in SMA patients, combined nusinersen after GT did not appear to add gain in motor function and older age is associated with prolonged corticosteroid use.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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