% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Cordts:298921,
      author       = {I. Cordts and C. Fuetterer and A. Wachinger and R. von
                      Heynitz and T. Kessler$^*$ and M. Freigang and A. L. Quinten
                      and B. Bjelica and S. Brakemeier and E. Hobbiebrunken and T.
                      Hagenacker and S. Petri and J. C. Koch and A. Hahn and P.
                      Lingor and M. Deschauer and R. Günther and M. Weiler and B.
                      Haller and E. Feneberg},
      title        = {{L}ong-{T}erm {D}ynamics of {CSF} and {S}erum
                      {N}eurofilament {L}ight {C}hain in {A}dult {P}atients {W}ith
                      5q {S}pinal {M}uscular {A}trophy {T}reated {W}ith
                      {N}usinersen.},
      journal      = {Neurology},
      volume       = {104},
      number       = {5},
      issn         = {0028-3878},
      address      = {Philadelphia, Pa.},
      publisher    = {Wolters Kluwer},
      reportid     = {DKFZ-2025-00357},
      pages        = {e213371},
      year         = {2025},
      abstract     = {The availability of disease-modifying therapies for
                      5q-associated spinal muscular atrophy (SMA) has heightened
                      the need to identify suitable biomarkers. This study
                      investigates neurofilament light chain (NfL) concentrations
                      during long-term nusinersen treatment in adult SMA.In a
                      retrospective study of prospectively collected data, NfL
                      concentrations in the CSF (cNfL) and serum (sNfL) were
                      measured in patients with SMA from 8 German centers and in
                      neurologic controls using a single-molecule array (Simoa)
                      assay. NfL concentrations and clinical characteristics,
                      including the clinical scores Hammersmith Functional Motor
                      Scale Expanded (HFMSE), Revised Upper Limb Module (RULM),
                      and Amyotrophic Lateral Sclerosis Functional Rating
                      Scale-Revised (ALSFRS-R), were analyzed for defined
                      treatment intervals (T1-T4 [loading phase until 4 months],
                      T5-T8 [until 23 months], T9-T12 [until 37 months], and
                      T13-T19 [until 60 months]). Linear mixed models with a
                      random intercept were used to assess the changes in NfL
                      levels during treatment, considering time and covariates as
                      fixed effects.One hundred thirteen adult patients with SMA
                      (median age 35, $46\%$ female), with a treatment duration of
                      maximum 60 months, and 52 controls were included. At
                      baseline, NfL concentrations were significantly higher in
                      SMA {cNfL median, 585 (interquartile range [IQR] 428-787)
                      pg/mL; sNfL, 11 (IQR 8-14) pg/mL} than in controls (cNfL,
                      420 [IQR 323-662] pg/mL; sNfL, 8 [IQR 6-12] pg/mL) (cNfL, p
                      = 0.021; sNfL, p = 0.030). Median differences for all
                      clinical scores were the highest for T5-T8 compared with the
                      loading phase (Δ HFMSE, 0.6 [IQR 0.1-1.4], p = 0.017; Δ
                      RULM, 0.9 [IQR 0.4-1.3], p < 0.001; Δ ALSFRS-R, 0.7 [IQR
                      0.4-1.0], p < 0.001), but not for subsequent intervals.
                      Longitudinal analysis revealed a significant decrease of NfL
                      concentrations during each treatment interval compared with
                      the loading phase (p < 0.05, respectively) except for sNfL
                      in T13-T19. Even among patients with no measurable clinical
                      improvement (Δ HFMSE ≤ 0), more than $50\%$ showed
                      declining cNfL and sNfL levels up to T13-T19.NfL decreased
                      during nusinersen treatment, suggesting its potential as a
                      pharmacodynamic response marker in adult SMA. However, in
                      patients without detectable clinical improvement, our study
                      cannot determine whether they represent a more sensitive
                      outcome measure or are not clinically meaningful.},
      keywords     = {Humans / Neurofilament Proteins: blood / Neurofilament
                      Proteins: cerebrospinal fluid / Male / Female / Adult /
                      Oligonucleotides: therapeutic use / Retrospective Studies /
                      Middle Aged / Muscular Atrophy, Spinal: drug therapy /
                      Muscular Atrophy, Spinal: blood / Muscular Atrophy, Spinal:
                      cerebrospinal fluid / Biomarkers: blood / Biomarkers:
                      cerebrospinal fluid / Young Adult / nusinersen (NLM
                      Chemicals) / Neurofilament Proteins (NLM Chemicals) /
                      neurofilament protein L (NLM Chemicals) / Oligonucleotides
                      (NLM Chemicals) / Biomarkers (NLM Chemicals)},
      cin          = {B320 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B320-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39946662},
      doi          = {10.1212/WNL.0000000000213371},
      url          = {https://inrepo02.dkfz.de/record/298921},
}