CC BY-NC-ND 4.0 · Journal of Pediatric Neurology 2022; 20(04): 252-257
DOI: 10.1055/s-0041-1731395
Original Article

Evaluation of Metabolic Effects of Nusinersen in Patients with Spinal Muscular Atrophy

Lena-Luise Becker
1   Department of Pediatric Neurology, Charité–Universitätsmedizin Berlin, Berlin, Germany
2   Center for Chronically Sick Children, Charité–Universitätsmedizin, Berlin, Germany
3   Institute for Cell Biology and Neurobiology, Charité–Universitätsmedizin Berlin, Berlin, Germany
,
Claudia Weiss
2   Center for Chronically Sick Children, Charité–Universitätsmedizin, Berlin, Germany
,
René Günther
4   Department of Neurology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
5   Deutsches Zentrum für Neurodegenerative Erkrankungen, Dresden, Germany
,
Andreas Hermann
4   Department of Neurology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
6   Department of Neurology, Translational Neurodegeneration Section, University Medical Center Rostock, Albrecht-Kossel, University of Rostock, Rostock, Germany
7   German Center for Neurodegenerative Diseases Rostock, Rostock, Germany
,
Manuela Theophil
8   Department of Pediatric Neurology, DRK Kliniken Berlin Westend, Berlin, Germany
,
Angela Hübner
9   Department of Pediatrics, Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Dresden, Germany
,
Martin Smitka
10   Department of Pediatric Neurology, Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Dresden, Germany
,
Maja von der Hagen
10   Department of Pediatric Neurology, Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Dresden, Germany
,
Angela M. Kaindl
1   Department of Pediatric Neurology, Charité–Universitätsmedizin Berlin, Berlin, Germany
2   Center for Chronically Sick Children, Charité–Universitätsmedizin, Berlin, Germany
3   Institute for Cell Biology and Neurobiology, Charité–Universitätsmedizin Berlin, Berlin, Germany
› Author Affiliations
Funding The study was funded by Charité – Universitätsmedizin Berlin and the German Research Foundation (DFG, SFB1315, FOR3004).

Abstract

Nusinersen is the first disease-modifying therapy for spinal muscular atrophy (SMA), but there are few data on potential long-term endocrinological and metabolic systemic effects of this novel treatment as well as metabolic alterations in SMA itself. In this retrospective and multicentric study, we analyzed anthropometric, endocrinological, and motor function data of 81 pediatric and adult patients with SMA1 to 3 undergoing treatment with nusinersen. In 39 patients (51%), we observed a slight increase in body mass index (BMI) centiles under treatment with nusinersen, especially in patients with SMA2 and in pediatric patients between 3.1 and 12 years. A correlation to the SMN2 copy number or motor function was not found. Additionally, length centiles decreased significantly under treatment. The results of longitudinal endocrinological assessments were interpreted as not clinically significant in most patients; in three patients, the signs of an altered glucose metabolism were present. Our study indicates a putative effect of treatment with nusinersen on BMI, which might be due to a conjoint effect of weight gain and reduction of height velocity, without evidence of correlation to increased muscle function. Further studies need to address specific effects of targeted therapies such as nusinersen or onasemnogene abeparvovec on body composition including fat and muscle mass.

Authors' Contributions

M.S. received compensations for presentations and training activities for Biogen. M.V.D.H. and C.W. received compensations for presentations and taking part in advisory boards from Biogen, Avexis and Sarepta. R.G. has received compensations for presentations/advisory boards from Biogen, and A.M.K. received compensations for taking part in advisory boards from Avexis and GW Pharma. A.H. has received honoraria for presentations/advisory boards from Desitin and Biogen, royalties from Elsevier Press and serves as an editorial board member of BMC neurology.


Supplementary Material



Publication History

Received: 17 December 2020

Accepted: 02 May 2021

Article published online:
03 July 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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