Journal Article

DZNE-2022-00474

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neurofilament proteins as a potential biomarker in chemotherapy-induced polyneuropathy.

Huehnchen, P. ; Schinke, C. ; Bangemann, N. ; Dordevic, A. D. ; Kern, J. ; Maierhof, S. K. ; Hew, L. ; Nolte, L. ; Körtvelyessy, P.DZNE* ; Göpfert, J. C. ; Ruprecht, K. ; Somps, C. J. ; Blohmer, J.-U. ; Sehouli, J. ; Endres, M.DZNE* ; Boehmerle, W.

2022
JCI Insight Ann Arbor, Michigan

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Please use a persistent id in citations: doi:10.1172/jci.insight.154395

Abstract: BACKGROUNDPaclitaxel chemotherapy frequently induces dose-limiting sensory axonal polyneuropathy. Given that sensory symptoms are challenging to assess objectively in clinical practice, an easily accessible biomarker for chemotherapy-induced polyneuropathy (CIPN) holds the potential to improve early diagnosis. Here, we describe neurofilament light chain (NFL), a marker for neuroaxonal damage, as a translational surrogate marker for CIPN.METHODSNFL concentrations were measured in an in vitro model of CIPN, exposing induced pluripotent stem cell-derived sensory neurons (iPSC-DSNs) to paclitaxel. Patients with breast or ovarian cancer undergoing paclitaxel chemotherapy, breast cancer control patients without chemotherapy, and healthy controls were recruited in a cohort study and examined before chemotherapy (V1) and after 28 weeks (V2, after chemotherapy). CIPN was assessed by the validated Total Neuropathy Score reduced (TNSr), which combines patient-reported symptoms with data from clinical examinations. Serum NFL (NFLs) concentrations were measured at both visits with single-molecule array technology.RESULTSNFL was released from iPSC-DSNs upon paclitaxel incubation in a dose- and time-dependent manner and was inversely correlated with iPSC-DSN viability. NFLs strongly increased in paclitaxel-treated patients with CIPN, but not in patients receiving chemotherapy without CIPN or controls, resulting in an 86% sensitivity and 87% specificity. An NFLs increase of +36 pg/mL from baseline was associated with a predicted CIPN probability of more than 0.5.CONCLUSIONNFLs was correlated with CIPN development and severity, which may guide neurotoxic chemotherapy in the future.TRIAL REGISTRATIONClinicalTrials.gov NCT02753036.FUNDINGDeutsche Forschungsgemeinschaft (EXC 257 NeuroCure), BMBF (Center for Stroke Research Berlin, 01 EO 0801), Animalfree Research, EU Horizon 2020 Innovative Medicines Initiative 2 Joint Undertaking (TransBioLine, 821283), Charité 3R - Replace - Reduce - Refine.

Keyword(s): Antineoplastic Agents: adverse effects (MeSH) ; Biomarkers (MeSH) ; Cohort Studies (MeSH) ; Humans (MeSH) ; Neurofilament Proteins (MeSH) ; Paclitaxel: adverse effects (MeSH) ; Peripheral Nervous System Diseases: chemically induced (MeSH) ; Peripheral Nervous System Diseases: diagnosis (MeSH) ; Polyneuropathies: chemically induced (MeSH) ; Polyneuropathies: diagnosis (MeSH) ; Adult stem cells ; Cancer ; Neuroscience ; Toxicology ; Antineoplastic Agents ; Biomarkers ; Neurofilament Proteins ; Paclitaxel

Note: (CC BY)

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Contributing Institute(s):

1. Clinical Neurophysiology and Memory (AG Düzel 3)
2. Coordinator of Clinical Research (AG Endres)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2022

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Database coverage:
; ; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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