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CC BY 4.0 · Arq Neuropsiquiatr 2024; 82(11): s00441791757
DOI: 10.1055/s-0044-1791757
Original Article

Type-1 spinal muscular atrophy cohort before and after disease-modifying therapies

Coorte de atrofia muscular espinhal tipo 1 antes e depois de terapias modificadoras da doença
Brenda Klemm Arci Mattos de Freitas Alves 
1   Universidade Federal do Rio de Janeiro, Pós-graduação em Saúde Materno-infantil, Rio de Janeiro RJ, Brazil.
,
Alexandra Prufer de Queiroz Campos Araujo 
2   Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Departamento de Pediatria, Rio de Janeiro RJ, Brazil.
,
Flávia Nardes dos Santos 
2   Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Departamento de Pediatria, Rio de Janeiro RJ, Brazil.
,
Márcia Gonçalves Ribeiro 
2   Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Departamento de Pediatria, Rio de Janeiro RJ, Brazil.
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Abstract

Background Spinal muscular atrophy (SMA-5q) is a neurodegenerative disease characterized by progressive muscle atrophy, hypotonia, and weakness, with SMA 1 presenting symptoms within the first 6 months of life. Disease-modifying therapies have been approved, with better outcomes with earlier treatment.

Objective To describe the safety and clinical efficacy of disease-modifying therapies based on SMN1 and SMN2 gene strategies concerning motor, respiratory, and bulbar function. Patients with SMA 1 were divided into 2 groups: those exclusively on nusinersen (group 1) and those transitioning to onasemnogene abeparvovec (OA) (group 2).

Methods Over 18 months, patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scale, developmental milestones, ventilation needs and duration, nutritional support needs, consistency of food, and signs of dysphagia. There were ten patients, divided between the groups; in group 1, the average age for starting nusinersen was 53.6 (12–115) months, and, in group 2, the age was 7 (1–12) months for nusinersen and 15.2 (10–19) months for OA.

Results Our results indicate that 70% of patients reached some motor milestones, with group 1 increasing by 10.2 points on the CHOP-INTEND scale, while group 2 increased by 33 points. Additionally, 90% of the patients experienced no respiratory decline, and 30% maintained oral feeding. No serious adverse effects or deaths were recorded.

Conclusion Both groups showed improvement in motor function and stabilization of respiratory and bulbar function, with the difference between the groups possibly being related to the earlier treatment initiation. Thus, the present study provides valuable insights into the real-world safety and clinical efficacy of disease-modifying therapies for SMA 1 patients.

Resumo

Antecedentes A atrofia muscular espinhal (AME-5q) é uma doença neurodegenerativa caracterizada por atrofia muscular progressiva, hipotonia e fraqueza. Na AME 1 os sintomas iniciam-se no primeiro semestre de vida. Terapias modificadoras de doença foram aprovadas e demonstram melhores resultados quanto mais cedo forem iniciadas.

Objetivo Descrever a segurança e a eficácia clínica das terapias modificadoras de doença quanto às funções motora, respiratória e bulbar. Os pacientes com AME 1 foram divididos em 2 grupos: os que faziam uso exclusivamente de nusinersena (grupo 1) e os que transacionaram para onasemnogene abeparvovec (OA) (grupo 2).

Métodos Durante 18 meses, os pacientes foram avaliados utilizando a escala Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), marcos do desenvolvimento, necessidade e duração da ventilação, necessidade de suporte nutricional, consistência dos alimentos e sinais de disfagia. Dividiram-se dez pacientes entre os grupos; no grupo 1, a idade média para início do nusinersena foi de 53,6 (12–115) meses e, no grupo 2, a idade foi de 7 (1–12) meses para o nusinersena e 15,2 (10–19) meses para OA.

Resultado Nossos resultados indicam que 70% dos pacientes atingiram algum marco motor, com o grupo 1 aumentando 10,2 pontos na escala CHOP-INTEND, e o grupo 2 aumentando 33. Ademais, 90% dos pacientes não apresentaram declínio respiratório e 30% mantiveram alimentação oral. Não houve efeitos adversos graves ou mortes.

Conclusão Ambos os grupos apresentaram melhoria na função motora e estabilização da função respiratória e bulbar, com a diferença entre os grupos sendo possivelmente relacionada com o início mais precoce do tratamento. Assim, este estudo fornece informações valiosas sobre a segurança e eficácia clínica destas terapias para pacientes com AME 1.

Keywords

Survival of Motor Neuron 1 Protein - Muscular Atrophy, Spinal - Genetic Therapy

Palavras-chave

Proteína 1 de Sobrevivência do Neurônio Motor - Atrofia Muscular Espinhal - Terapia Genética

Authors' Contributions

BKAMFA: data collection, formal analysis, writing – original draft, and writing – review & and editing; APQCA, FNS, MGR: conceptualization, methodology, critical review, and writing – review & editing. All authors discussed the results and contributed to the final manuscript.


Editor-in-Chief: Hélio A. G. Teive.


Associate Editor: Edmar Zanoteli.




Publikationsverlauf

Eingereicht: 10. April 2024

Angenommen: 02. August 2024

Artikel online veröffentlicht:
06. November 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
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Bibliographical Record
Brenda Klemm Arci Mattos de Freitas Alves, Alexandra Prufer de Queiroz Campos Araujo, Flávia Nardes dos Santos, Márcia Gonçalves Ribeiro. Type-1 spinal muscular atrophy cohort before and after disease-modifying therapies. Arq Neuropsiquiatr 2024; 82: s00441791757.
DOI: 10.1055/s-0044-1791757
 

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