To determine the diagnostic and monitoring value of serum neurofilament light chain (NfL) in spinal muscular atrophy (SMA).
We measured serum NfL in 46 SMA patients at baseline and over 14 months of treatment with the antisense-oligonucleotide (ASO) nusinersen using the ultrasensitive single molecule array (Simoa) technology. Serum NfL levels of SMA patients were compared to controls and related to cerebrospinal fluid (CSF) NfL, blood-CSF barrier function quantified by the albumin blood/CSF ratio (Qalb) and motor scores (Hammersmith Functional Motor Scale Expanded, HFMSE; Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, ALSFRS-R).
Serum NfL levels of SMA patients were in the range of controls (p = 0.316) and did not correlate with CSF NfL (ρ = 0.302, p = 0.142) or Qalb (ρ = − 0.160, p = 0.293). During therapy, serum NfL levels were relatively stable with notable concentration changes in single SMA patients, however, within the control range. Higher NfL levels were associated with worse motor performance in SMA (baseline: HFMSE ρ = − 0.330, p = 0.025, ALSFRS-R ρ = − 0.403, p = 0.005; after 10 months: HFMSE ρ = − 0.525, p = 0.008, ALSFRS-R ρ = − 0.537, p = 0.007), but changes in motor scores did not correlate with changes in serum NfL.
Diagnostic and monitoring performance of serum NfL measurement seems to differ between SMA subtypes. Unlike to SMA type 1, in adolescent and adult SMA type 2 and 3 patients, neurodegeneration is not reflected by increased NfL levels and short-term therapeutic effects cannot be observed. Long-term follow-up has to be performed to see if even low levels of NfL might be good prognostic markers.
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The authors thank all patients for participating in this study. Thanks for technical assistance to Dagmar Schattauer, Sandra Hübsch, Alice Pabst and Mehtap Bulut-Karac.
The study was supported in part by grants from the German Federal Ministry of Education and Research [project FTLDc 01GI1007A, MND-Net 01GI0704]; PreFrontAls [01ED1512]; the ALS association; the Thierry Latran Foundation; and the Charcot Foundation for ALS Research. AH is supported by the Hermann und Lilly Schilling-Stiftung.
Conflicts of interest
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CDW has received honoraria from Biogen as an Advisory board member and for lectures and as a consultant from Hoffmann-La Roche. She also received travel expenses from Biogen. PS, SW, KW and MRAS report no disclosures. RG has received honoraria from Biogen as an Advisory board member. JCK has received financial research support form TEVA Pharmaceuticals and honoraria as speaker/consultant for AbbVie, Allergan, Biogen, Ipsen and AveXis/Novartis. PL has received financial research support from TEVA Pharmaceuticals and honoraria as speaker/consultant for AbbVie, Atheneum Partners, BIAL, Desitin, Licher MT, Medtronic, Novartis. ZU has received honoraria from Biogen as a consultant. BW has received honoraria from Biogen for a lecture. AO has received honoraria from Biogen as a consultant. OSK has received honoraria as a speaker/consultant and/or funding for travel expenses from the Deutsche Gesellschaft für Muskelkranke (DGM e.V.), Novartis, Biogen GmbH, the Jain Foundation. She received academic research support by Ludwig-Maximilians-University of Munich, FoeFoLe program, Reg.-No. 747, 11/11–05/13, and MHH Young Faculty Program, 2018–2020 as well as research support by foundations and societies by the Friedrich-Baur-GmbH, Burgkunstadt 12/13–12/15 and the Deutsche Gesellschaft für Muskelkranke (DGM e.V.), 2019–20. ACL received financial research support from AB Science, Biogen Idec, Cytokinetics, GSK, Orion Pharma, Novartis, TauRx Therapeutics Ltd. and TEVA Pharmaceuticals. He also has received honoraria as a consultant from Mitsubishi, Orion Pharma, Novartis, Teva and as an Advisory board member of Biogen and Hoffmann-La Roche. SP has received honoraria as speaker/consultant from Biogen Idec, Novartis, Cytokinetics, TEVA Pharmaceuticals, Desitin. AH has received honoraria from Biogen and Desitin as a consultant. MO received honoraria as consultant from Biogen, Axon and Fujirebio.
The study was approved by the local ethics committees of the centers involved in Ulm, Dresden, Göttingen and Hannover (approval number at central study center at Ulm University 19/12; 2012) and all patients or their relatives (legal guardian) gave informed written consent to participate in the study.
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Wurster, C.D., Steinacker, P., Günther, R. et al. Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen. J Neurol 267, 36–44 (2020) doi:10.1007/s00415-019-09547-y