Use of European registries to characterise the changing landscape of disease progression and treatment of spinal muscular atrophy (SMA): opportunities, pitfalls and challenges

@article{deltour2026european,
  title = {{Use of European registries to characterise the changing landscape of disease progression and treatment of spinal muscular atrophy (SMA): opportunities, pitfalls and challenges}},
  author = {Nicolas Deltour and Seung Yeon Lee and Elizabeth M. Garry and Liza R. Gibbs and Shane McElwee and Renee M. Sajedian and Emmanuelle Jacquot and Siyana Kurteva and Anabel Ferreras and Annie Poll and Ben Porter and Rhian Davies and Jack Kennedy and Maggie C. Walter and Simone Thiele and Marlène Jagut and Marjan Cosyns and Liesbeth de Waele and Nicolas Deconinck and Jana Haberlová and Lenka Mokrá and Maria Grazia Cattinari and Eduardo F. Tizzano and Chiara Marini-Bettolo and Lindsay Murphy and Anne-Berit Ekström and Miriam Rodrigues and Anna Ambrosini and Victoria Hodgkinson and Michela Guglieri and Mencia de Lemus Belmonte and Kieran C. Breen and Laurent Servais and Aurore Daron and Aurore Daron and Stephanie Delstanche and Laura Vanden Brande and Alain Maertens de Noordhout and Stéphanie Paquay and Van den Bergh and Vinciane Van Parys and Nicolas Dubuisson and Gauthier Remiche and Florence Christiaens and Jonathan Baets and Alicia Alonso-Jimenez and Diane Beysen and Véronique Bissay and Nathalie Smeets and Karine Pelc and Katrien De Braekeleer and Jan De Bleecker and Arnaud Vanlander and Sarah Herdewyn and Kristl Claeys and Geertrui Peirens and Philip Van Damme and Anna-Karin Kroksmark and Olesja Parmová and Lenka Juříková},
  journal = {Orphanet Journal of Rare Diseases},
  year = {2026},
  month = aug,
  doi = {10.1186/s13023-026-04491-3},
  url = {https://doi.org/10.1186/s13023-026-04491-3},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Use of European registries to characterise the changing landscape of disease progression and treatment of spinal muscular atrophy (SMA): opportunities, pitfalls and challenges
AU  - Nicolas Deltour
AU  - Seung Yeon Lee
AU  - Elizabeth M. Garry
AU  - Liza R. Gibbs
AU  - Shane McElwee
AU  - Renee M. Sajedian
AU  - Emmanuelle Jacquot
AU  - Siyana Kurteva
AU  - Anabel Ferreras
AU  - Annie Poll
AU  - Ben Porter
AU  - Rhian Davies
AU  - Jack Kennedy
AU  - Maggie C. Walter
AU  - Simone Thiele
AU  - Marlène Jagut
AU  - Marjan Cosyns
AU  - Liesbeth de Waele
AU  - Nicolas Deconinck
AU  - Jana Haberlová
AU  - Lenka Mokrá
AU  - Maria Grazia Cattinari
AU  - Eduardo F. Tizzano
AU  - Chiara Marini-Bettolo
AU  - Lindsay Murphy
AU  - Anne-Berit Ekström
AU  - Miriam Rodrigues
AU  - Anna Ambrosini
AU  - Victoria Hodgkinson
AU  - Michela Guglieri
AU  - Mencia de Lemus Belmonte
AU  - Kieran C. Breen
AU  - Laurent Servais
AU  - Aurore Daron
AU  - Aurore Daron
AU  - Stephanie Delstanche
AU  - Laura Vanden Brande
AU  - Alain Maertens de Noordhout
AU  - Stéphanie Paquay
AU  - Van den Bergh
AU  - Vinciane Van Parys
AU  - Nicolas Dubuisson
AU  - Gauthier Remiche
AU  - Florence Christiaens
AU  - Jonathan Baets
AU  - Alicia Alonso-Jimenez
AU  - Diane Beysen
AU  - Véronique Bissay
AU  - Nathalie Smeets
AU  - Karine Pelc
AU  - Katrien De Braekeleer
AU  - Jan De Bleecker
AU  - Arnaud Vanlander
AU  - Sarah Herdewyn
AU  - Kristl Claeys
AU  - Geertrui Peirens
AU  - Philip Van Damme
AU  - Anna-Karin Kroksmark
AU  - Olesja Parmová
AU  - Lenka Juříková
PY  - 2026
DA  - 2026/08/05
JO  - Orphanet Journal of Rare Diseases
DO  - 10.1186/s13023-026-04491-3
UR  - https://doi.org/10.1186/s13023-026-04491-3
AB  - Background: Spinal muscular atrophy (SMA), a rare neurodegenerative disorder with an estimated prevalence of 1 in 14,300 live births and is the leading genetic cause of mortality in infants and children. Since the approval of new disease-modifying treatments (DMTs; nusinersen (Spinraza) in 2017, onasemnogene abeparvovec-xioi (Zolgensma) in 2020, and oral risdiplam (Evrysdi) in 2021), studies have reported changes in disease progression. This retrospective cohort study analyzed six SMA registries within the TREAT-NMD network, selected via feasibility assessment. These registries comprise data from nine European countries: three clinician-based registries (Belgium, Czech Republic plus Slovakia, Sweden) and three patient-based registries (Germany plus Austria, Spain, United Kingdom plus Ireland) covering the period spanning April 2008 and May 2023.  Results: Among 2,188 SMA patients with genetically confirmed 5q SMA, the most common SMA subtype was type 2 (SMA2; n = 914, 41.8%) followed by types 3 (SMA3; n = 779, 35.6%) and 1 (SMA1; n = 432, 19.7%). Treatment with at least one DMT was reported among 1,321 (60.4%) of patients and increased over time; nusinersen was the most common DMT (N = 1,003; 75.9%) followed by risdiplam (N = 403; 30.5%) and onasemnogene (N = 101; 7.6%). Among treated patients with SMA1, SMA2, and SMA3, best functional status reported was “sitter” for 36.6%, 60.9%, and 5.3%, and “walker” for 12.0%, 24.6%, and 87.8%, respectively. For SMA1 and SMA2, best motor milestone reported was “sit without support” for 27.2% and 38.0%, and “roll onto side” for 18.5% and 2.0%; for SMA3, “climb stairs” was reported for 63.4% and “walk 10 metres without assistance” reported for 19.3%. Missingness of functional status and motor milestone among patients with SMA1, SMA2, and SMA3 was lower among those treated (27.9%, 8.5%, and 5.5%) as accounted for almost all never treated (100%, 97.8%, and 100%).  Conclusions: Functional status and motor milestones were well captured after treatment but rarely reported before treatment or in patients who were never treated, limiting evaluation of treatment related changes. Areas of improvement for registry data quality have been identified to reduce data missingness, increase standardisation, and consequently enhance their ability to inform regulatory decision making.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13023-026-04491-3.
SN  - 1750-1172
ER  -