Nusinersen for children with type I spinal muscular atrophy: 4 years' clinical experience in Turkish cohort.

BACKGROUND

SMA Type 1 is the most severe form of spinal muscular atrophy with early symptom onset, limited motor development, and poor prognosis. Recent genetic-based therapies, such as nusinersen, have transformed disease outcomes. We aimed to evaluate the long-term effects of nusinersen on motor, bulbar, and respiratory functions in both symptomatic and presymptomatic SMA Type 1 patients over a period of up to 4 years.

METHODS

This prospective, non-interventional study included 310 patients with genetically confirmed spinal muscular atrophy at 24 pediatric neurology centers in Turkey. Patients treated with nusinersen were divided into five age-based cohorts at treatment initiation: Cohort A (0-3 months), Cohort B (4-6 months), Cohort C (7-12 months), Cohort D (13-24 months), and Cohort E (>24 months). Efficacy was assessed using the CHOP-INTEND and WHO Motor Milestone Scale. This study also analyzed the respiratory support needs, gastrostomy requirements, and mortality rates across cohorts.

RESULTS

Patients treated before 12 months of age showed the most significant improvements in motor milestones, with 58.7% of Cohort A achieving independent sitting. CHOP-INTEND scores increased notably in all cohorts, with the largest improvement observed in Cohort A (93.5%). Ventilator and gastrostomy requirements decreased in the early treated cohorts. Adverse events were rare, with one discontinuation due to hydrocephalus. The overall mortality rate was 21.3%, with most of the deaths occurring within the first year.

INTERPRETATION: Nusinersen treatment initiated before 12 months of age, especially before 3 months of age, yielded the most favorable motor outcomes in patients with SMA type 1. Early initiation is associated with improved motor milestones and reduced need for ventilatory support. However, no significant improvements were observed in the bulbar function or in patients requiring extensive respiratory support.