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. 2025 Mar 27:16:1541507.
doi: 10.3389/fneur.2025.1541507. eCollection 2025.

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

Ömer Bektaş  1 , Murat Gülşen  2 , Onur Burak Dursun  2 , Ahmet Tekin  3 , Deniz Yüksel  4 , Ercan Demir  5 , Gülten Öztürk  6 , Sema Saltık  7 , Özlem Hergüler  8 , Ayşe Aysima Özçelik  9 , Hüseyin Tan  10 , Bilge Özgör  11 , Arzu Ekici  12 , Merve Feyza Yüksel  1 , Süleyman Şahin  1 , Özgür Duman  13 , Mustafa Kömür  14 , Figen Baydan  15 , Edibe Pembegül Yıldız  16 , Bülent Kara  17 , Uluç Yiş  18 , Seda Kanmaz  19 , Kürşat Bora Çarman  20 , Elif Acar Arslan  21 , Mehmet Canpolat  22 , Ahmet Sami Güven  23 , Gökçen Öztuncer  24 , Aycan Ünalp  25 , Didem Ardıçlı  26 , Aynur Ayşe Karaduman  27 , Gökmen Zararsız  28 , Gülhis Deda  29 ; Turkish SMA Study Group
Collaborators, Affiliations

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

Ömer Bektaş et al. Front Neurol. .

Abstract

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.

Keywords: SMA type 1; bulbar function; motor function; nusinersen; presymptomatic; severe symptomatic; spinal muscular atrophy; ventilatory.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Probability of gaining the ability to sit without support. The probability of gaining the ability to sit without support in Cohort A (red), Cohort B (khaki), Cohort C (green), Cohort D (blue), and Cohort E (purple). Numbers at risk are listed for dedicated time points.
Figure 2
Figure 2
Respiratory changes before and after treatment. IMV, Invasive mechanical ventilation.
Figure 3
Figure 3
Feeding status before and after treatment.
See this image and copyright information in PMC

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