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@ARTICLE{Steffke:282590,
      author       = {Steffke, Christina and Baskar, Karthik and Bachhuber,
                      Franziska and Wiesenfarth, Maximilian and Dorst, Johannes
                      and Schuster, Joachim and Schöberl, Florian and Reilich,
                      Peter and Regensburger, Martin and German, Alexander and
                      Günther, René and Vidovic, Maximilian and Petri, Susanne
                      and Meyer, Thomas and Hagenacker, Tim and Grosskreutz,
                      Julian and Weyen, Ute and Weydt, Patrick and Haarmeier,
                      Thomas and Lingor, Paul and Wolf, Joachim and Hermann,
                      Andreas and Prudlo, Johannes and Günther, Kornelia and
                      Knehr, Antje and Elmas, Zeynep and Uzelac, Zeljko and
                      Witzel, Simon and Ruf, Wolfgang Philipp and Freischmidt,
                      Axel and Ho, Ritchie and Ludolph, Albert C and Weishaupt,
                      Jochen H and Tumani, Hayrettin and Oeckl, Patrick and
                      Brenner, David and Catanese, Alberto},
      title        = {{T}argeted {P}roteomics upon {T}reatment with {T}ofersen
                      {I}dentifies {N}ovel {R}esponse {M}arkers for {S}uperoxide
                      {D}ismutase 1-{L}inked {A}myotrophic {L}ateral {S}clerosis.},
      journal      = {Annals of neurology},
      volume       = {98},
      number       = {6},
      issn         = {0364-5134},
      address      = {Hoboken, NJ},
      publisher    = {Wiley-Blackwell},
      reportid     = {DZNE-2025-01350},
      pages        = {1318 - 1334},
      year         = {2025},
      abstract     = {Tofersen is the first effective and approved therapy for
                      superoxide dismutase 1 (SOD1)-associated amyotrophic lateral
                      sclerosis (ALS [SOD1-ALS]). Following treatment with
                      tofersen, neurofilament levels in patients' cerebrospinal
                      fluid (CSF) and serum seem to respond earlier than clinical
                      parameters. This evidence prompted us to hypothesize that
                      this novel treatment could provide an opportunity to
                      identify additional biomarkers responsive to therapy in
                      SOD1-ALS.We investigated a panel of 120 neural, glial, and
                      inflammatory markers in CSF and serum samples longitudinally
                      collected from a total of 28 SOD1-ALS patients at baseline,
                      and after 3, 6 and 12 months of treatment with tofersen,
                      followed by validation with conventional methodology.We
                      identified a set of proteins, including neurofilament light
                      chain, neurofilament heavy chain, amyloid-beta 1-40 and
                      amyloid-beta 1-42, neuropeptide Y (NPY), and ubiquitin
                      C-terminal hydrolase L1 (UCHL1), whose CSF levels both
                      differed between SOD1-ALS and the control group, and were
                      responsive to tofersen at 3 and 6 months after treatment
                      initiation. Another group of markers, including the
                      neuropentraxin (NPTX) family members NPTX1, NPTX2 and NPTXR,
                      did not separate untreated SOD1-ALS from controls, but was
                      responsive to tofersen. At 12 months on tofersen the levels
                      of neurofilament light chain, neurofilament heavy chain,
                      NPTX1, NPTX2, and NPTXR remained reduced compared with
                      baseline, and correlated with the clinical response to
                      tofersen. Consistent with increasing CSF pleocytosis and
                      intrathecal immunoglobulin production, inflammatory markers
                      were significantly increased after 12 months of
                      treatment.Our results highlight a complex, time-dependent
                      differential response of CSF biomarkers to tofersen
                      treatment, and may pave the way for developing a panel of
                      responsive proteins to make biomarker endpoints more robust
                      in clinical trials for SOD1-ALS and beyond. ANN NEUROL
                      2025;98:1318-1334.},
      keywords     = {Humans / Amyotrophic Lateral Sclerosis: drug therapy /
                      Amyotrophic Lateral Sclerosis: cerebrospinal fluid /
                      Amyotrophic Lateral Sclerosis: genetics / Amyotrophic
                      Lateral Sclerosis: blood / Male / Female / Middle Aged /
                      Proteomics: methods / Superoxide Dismutase-1: genetics /
                      Biomarkers: cerebrospinal fluid / Biomarkers: blood / Aged /
                      Adult / Neurofilament Proteins: cerebrospinal fluid /
                      Longitudinal Studies / Superoxide Dismutase-1 (NLM
                      Chemicals) / Biomarkers (NLM Chemicals) / SOD1 protein,
                      human (NLM Chemicals) / Neurofilament Proteins (NLM
                      Chemicals) / neurofilament protein L (NLM Chemicals)},
      cin          = {AG Böckers / Clinical Study Center (Ulm) / AG Falkenburger
                      / Clinical Research (Bonn) / Clinical Research (Munich) / AG
                      Hermann / AG Teipel / AG Danzer / AG Öckl},
      ddc          = {610},
      cid          = {I:(DE-2719)1910002 / I:(DE-2719)5000077 /
                      I:(DE-2719)1710012 / I:(DE-2719)1011001 / I:(DE-2719)1111015
                      / I:(DE-2719)1511100 / I:(DE-2719)1510100 /
                      I:(DE-2719)5000072 / I:(DE-2719)5000073},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40781905},
      doi          = {10.1002/ana.70025},
      url          = {https://pub.dzne.de/record/282590},
}