Frontiers in Neurology (Mar 2025)

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

  • Ömer Bektaş,
  • Murat Gülşen,
  • Onur Burak Dursun,
  • Ahmet Tekin,
  • Deniz Yüksel,
  • Ercan Demir,
  • Gülten Öztürk,
  • Sema Saltık,
  • Özlem Hergüler,
  • Ayşe Aysima Özçelik,
  • Hüseyin Tan,
  • Bilge Özgör,
  • Arzu Ekici,
  • Merve Feyza Yüksel,
  • Süleyman Şahin,
  • Özgür Duman,
  • Mustafa Kömür,
  • Figen Baydan,
  • Edibe Pembegül Yıldız,
  • Bülent Kara,
  • Uluç Yiş,
  • Seda Kanmaz,
  • Kürşat Bora Çarman,
  • Elif Acar Arslan,
  • Mehmet Canpolat,
  • Ahmet Sami Güven,
  • Gökçen Öztuncer,
  • Aycan Ünalp,
  • Didem Ardıçlı,
  • Aynur Ayşe Karaduman,
  • Gökmen Zararsız,
  • Gülhis Deda,
  • Turkish SMA Study Group,
  • Ömer Bektaş,
  • Murat Gülşen,
  • Onur Burak Dursun,
  • Ahmet Tekin,
  • Deniz Yüksel,
  • Ercan Demir,
  • Gülten Öztürk,
  • Sema Saltık,
  • Özlem Hergüler,
  • Ayşe Aysima Özçelik,
  • Hüseyin Tan,
  • Bilge Özgör,
  • Arzu Ekici,
  • Merve Feyza Yüksel,
  • Süleyman Şahin,
  • Özgür Duman,
  • Mustafa Kömür,
  • Figen Baydan,
  • Edibe Pembegül Yıldız,
  • Bülent Kara,
  • Uluç Yiş,
  • Seda Kanmaz,
  • Kürşat Bora Çarman,
  • Elif Acar Arslan,
  • Mehmet Canpolat,
  • Ahmet Sami Güven,
  • Gökçen Öztuncer,
  • Aycan Ünalp,
  • Didem Ardıçlı,
  • Aynur Ayşe Karaduman,
  • Gökmen Zararsız,
  • Nurşah Yeniay Süt,
  • Olcay Ünver,
  • Tuğçe Damla Dilek,
  • Eif Yıldırım,
  • Faruk İncecik,
  • Meral Karadağ,
  • Mehmet Fatih Bütün,
  • Burçin Gönüllü Polat,
  • Yiğithan Güzin,
  • Mehmet Akif Kılıç,
  • Adnan Deniz,
  • Gamze Sarıkaya Uzan,
  • Sanem Yılmaz Keskin,
  • Fatih M. Özdemir,
  • Coşkun Yarar,
  • Nihal Yıldız,
  • Hamit Acer,
  • Hüseyin Çaksen,
  • Seren Aydın,
  • Pakize Karaoğlu,
  • Ayşe Neşe Çıtak,
  • Tanıl Kendirli,
  • Birkan Sonel Tur,
  • Gülcan Akyüz,
  • Ceren Bibinoğlu Amirov,
  • Gülen Gül Mert,
  • Mahmut Aslan,
  • Şenay Haspolat,
  • Özlem Ersoy,
  • Osman Kipoğlu,
  • Defne Alikılıç,
  • Hasan Tekgül,
  • Ülkühan Kaya,
  • Arife Derda Yücel Şen,
  • Pınar Özkan Kart,
  • Hüseyin Per,
  • Ayşe Aksoy,
  • Ünsal Yılmaz,
  • Serap Teber,
  • Özben Akıncı Göktaş,
  • Dilşad Türkdoğan,
  • Fitnat Uluğ,
  • Serap Bilge,
  • Orhan Coşkun,
  • Merve Öztürk,
  • Esra Atmaca,
  • Ali Cansu,
  • Hakan Gümüş,
  • Evrim Karadağ Saygı,
  • Ömer Karaca,
  • Serdal Güngör,
  • Nazan Çobanoğlu,
  • Melek Sezgin,
  • Miraç Yıldırım,
  • Yasemin Gökdemir,
  • Esma Şengenç,
  • Yılmaz Zindar,
  • Özlem Yayıcı,
  • Serkan Köken,
  • Mesut Güngör,
  • Serkan Kırık,
  • Meltem Çobanoğulları Direk,
  • Gülhis Deda

DOI
https://doi.org/10.3389/fneur.2025.1541507
Journal volume & issue
Vol. 16

Abstract

Read online

BackgroundSMA 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.MethodsThis 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.ResultsPatients 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.InterpretationNusinersen 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