Nusinersen recently became available as the first treatment for Spinal Muscular Atrophy (SMA) and data on its effectiveness and safety in adult SMA patients are still scarce.
We evaluated the effectiveness and safety of nusinersen treatment during 14 months in 16 adult patients with SMA types 3 and 4 in a prospective study, and retrospectively detailed the natural history of 48 adult SMA patients types 2, 3 and 4.
Hand grip strength (p = 0.03), hand motor function (p = 0.04) as assessed by a sub-score of the Revised Upper Limb Module (RULM) and the Medical Research Council (MRC) sum score (p = 0.04) improved significantly at month 14. Importantly, the MRC sum score had declined significantly (p < 0.01) prior to start of treatment in these patients. A minimal clinically important difference (MCID) in the Hammersmith Functional Motor Scale Expanded (HFMSE) and RULM scores was achieved in 31% and 50% of the patients, respectively, but the mean changes from baseline failed to reach significance. Forced Vital Capacity (FVC) transiently increased at month 6 (p = 0.01), whereas the Peak Expiratory Flow (PEF) did not. The Activity Limitations scale declined significantly prior to start of treatment (p < 0.01) and showed an improvement with nusinersen which was not significant. The safety evaluation did not reveal serious adverse events and no signs of nephrotoxicity or antisense oligonucleotide (ASO)-mediated inflammation.
We conclude that hand grip strength and hand motor function, as well as MRC sum scores improved significantly in nusinersen-treated adult patients with SMA types 3 and 4.
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The supporting datasets analysed during the current study and the RStudio code used for statistical analyses are available from the corresponding author on reasonable request.
Spinal Muscular Atrophy
Survival of motor neuron protein
Belgian Federal Agency for Medicines and Health Products
Medical Research Council
Forced Vital Capacity
Peak Expiratory Flow
Six-minute walk distance
Continuous positive airway pressure
Obstructive sleep apnoea syndrome
Hammersmith Functional Motor Scale Expanded
Revised Upper Limb Module
36-Item Short Form Health Survey
Activity Limitations scale
Patient-reported outcome measure
Minimal clinically important difference
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The authors thank the patients for their participation in the study. They are grateful to the colleagues from the Radiology Department at UZ Leuven for their imaging support during some of the nusinersen injections. They thank Eveline Dewaege, Elise Lenaerts, Chris Schrevens, Kimberly Tielens, Cindy Thys, Leonie Vandenhoudt, Ann Van Der Vennet and Marielle Verbeek for their administrative and/or technical support. KGC is Chairholder of the Emil von Behring Chair for Neuromuscular and Neurodegenerative Disorders by CSL Behring. KGC is member of the European Reference Network for Rare Neuromuscular Diseases (ERN Euro-NMD) and of the European Reference Network for Rare Neurological Diseases (ERN-RND).
This study was partially funded by Biogen.
Conflicts of interest
KGC received advisory board honoraria from Alnylam, Biogen, CSL Behring, Sanofi-Genzyme and travel reimbursement from Sanofi-Genzyme, unrelated to this work. The other authors report no conflicts of interest.
Written informed consent was obtained from the patients. Both the Ethics Committee Research UZ/KU Leuven and the Belgian Federal Agency for Medicines and Health Products (FAGG) approved the study (EudraCT-nr: 2019-005007-40), which has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
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De Wel, B., Goosens, V., Sobota, A. et al. Nusinersen treatment significantly improves hand grip strength, hand motor function and MRC sum scores in adult patients with spinal muscular atrophy types 3 and 4. J Neurol (2020). https://doi.org/10.1007/s00415-020-10223-9
- Muscle strength
- Outcome measures
- Natural history