Dados do Trabalho

Título

EXPERIENCE OF A NEUROMUSCULAR CENTER IN PRE-SYMPTOMATIC SPINAL MUSCULAR ATROPHY TREATMENT

Introdução

Patients with 5q Spinal Muscular Atrophy (5q-SMA) can be diagnosed in a pre-symptomatic phase through newborn screening or when there is a sibling with SMA. Early diagnosis enables prompt intervention and improves patient outcomes.

Objetivo

To describe the experience of a neuromuscular center in the treatment of pre-symptomatic 5q-SMA patients and to analyze the clinical aspects during a follow-up period up to 60 months (range 2-60; average 17,66 months).

Método

Six 5q-SMA patients started treatment in a pre-symptomatic phase and have been monitored in a neuromuscular center in São Paulo-Brazil from August 2019 to July 2024. Neurological examination, motor scale and respiratory assessments have been performed by a multidisciplinar team at the diagnosis, every 3 months during the first year of follow-up and every 6 months thereafter. Informations on adverse effects have also been collected.

Resultados

All six pre-symptomatic patients had homozygous deletion of SMN1 gene and 2 copies of SMN2. Four patients were diagnosed by newborn screening and started risdiplam between 25 and 29 days of age (mean 26,75 days). One of them started risdiplam recently and remains asymptomatic at 3 months old, but still does not have a comparative motor scale. The 3 other risdiplam-treated patients achieved maximum score on Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) at 4 months old. All risdiplam-treated patients have adequate development for their age, but two of them switched treatment to zolgensma at 6 and 9 months old because it is a single dose therapy. Two patients were younger siblings of SMA patients and started nusinersen at 2 and 7 days old, but both changed treatment to zolgensma because of limb weakness. One of them received zolgensma at 5 months old, reached maximum CHOP INTEND score at 6 months old and started walking at 16 months old. The other patient received zolgensma at 18 months old, reached maximum CHOP INTEND score at 1 year old and started walking at 22 months old. None of the patients presented dysphagia or need for ventilatory support. Patients who received zolgensma presented these adverse effects: one had fever and vomiting, one thrombocytopenia and two elevated hepatic transaminases. One patient who received risdiplam had anemia.

Conclusão

This real-world data showed results similar to those from clinical trials and underscore the importance of early diagnosis and intervention.

Referências

Aragon-Gawinska, K.; Mouraux, C.; Dangouloff, T.; Servais, L. Spinal Muscular Atrophy Treatment in Patients Identified by Newborn Screening—A Systematic Review. Genes 2023, 14, 1377. https://doi.org/10.3390/genes14071377
Motyl AAL, Gillingwater TH. Timing is everything: Clinical evidence supports pre-symptomatic treatment for spinal muscular atrophy. Cell Rep Med. 2022 Aug 16;3(8):100725. doi: 10.1016/j.xcrm.2022.100725.

Palavras Chave

Spinal muscular atrophy; pre-symptomatic; therapy