Evidence map›Paper›PMID 42139087›Full record

ArticleSleep2026

Hypocretin-1/orexin-A fragment1-16 as a potential surrogate marker for diagnosing narcolepsy type 1.

Elena S Wenz, Jean-Christophe Prost, Sophie Braga-Lagache, Gabriela M Mäder, Jan D Warncke, Martin Luginbühl, Patrick Y Wuethrich, Friedrich Lersch, Christoph Schankin, Irina Filchenko and 9 more

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Article in Sleep, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

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No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

19 authors.

Elena S WenzDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.ORCID 0000-0002-6231-3358
Jean-Christophe ProstDepartment of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Sophie Braga-LagacheDepartment for Biomedical Research, Core Facility Proteomics & Mass Spectrometry, University of Bern, Bern, Switzerland.
Gabriela M MäderDepartment of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Jan D WarnckeDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.ORCID 0000-0001-6852-4191
Martin LuginbühlDepartment of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Patrick Y WuethrichDepartment of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Friedrich LerschDepartment of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Christoph SchankinDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Irina FilchenkoDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Livia FregolenteDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Kseniia ZubDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
iSPHYNCS consortium
Seiji NishinoSleep and Circadian Neurobiology Laboratory, School of Medicine, Stanford University, Stanford, CA, United States.ORCID 0000-0003-3959-2886
Carlo R LargiadèrDepartment of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Manfred HellerDepartment for Biomedical Research, Core Facility Proteomics & Mass Spectrometry, University of Bern, Bern, Switzerland.
Mehdi TaftiDepartment of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
Markus H SchmidtDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.ORCID 0000-0002-3299-1318
Claudio L A BassettiDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

STUDY

objectivesLoss of cerebrospinal fluid (CSF) hypocretin-1/orexin-A (Hcrt-1) immunoreactivity is a biomarker for narcolepsy type 1 (NT1). The current radioimmunoassay (RIA) does not allow precise quantification, limiting the assessment of disease severity and evolution. This study aimed to reproduce previously proposed workflows to quantify Hcrt-1 and Hcrt-2 by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), identify RIA antibody targets, and to compare two purification methods in their ability to identify patients with NT1.

methodsSolid phase extraction (SPE) and LC-MS/MS measurements of Hcrt-1 and -2 levels from 10 NT1 patients and 21 controls were implemented based on existing literature. Immunoprecipitation (IP) with magnetic beads coupled to the RIA antibody (Phoenix) was performed and peptides identified by MS. Finally, Hcrt-1 (full-length) and Hcrt-1 fragment1-16 levels were analyzed in 4 patients and 4 controls prepared from both workflows by nano-LC coupled to high-resolution mass spectrometry.

resultsDespite linear calibration curves for Hcrt-1 and Hcrt-2 (R2 > 0.99) could be assessed with LC-MS/MS, full-length Hcrt-1 concentrations were at the low end of the calibration curve with slightly lower levels in NT1 (p = 0.04). Hcrt-2 was undetectable. The discovery experiment with IP most reliably identified Hcrt-1 fragment1-16. SPE revealed much higher concentrations than IP. Hcrt-11-16-levels allowed distinguishing patients and controls after SPE and IP, whereas full-length Hcrt-1-levels after IP did not.

conclusionsHcrt-11-16 appears stable and abundant in CSF of controls, allows identification of patients with NT1 and is a promising surrogate marker. SPE seems more suitable for further method validation in clinical routine. Statement of Significance This proof-of-concept study is a systematic approach to the mass-spectrometric quantification of the neuropeptide hypocretin-1/orexin-A (Hcrt-1) in the cerebrospinal fluid, since the currently used radioimmunoassay (RIA) does not allow precise quantification. It reveals Hcrt-1 N-terminal derived fragment1-16 as one main target of the RIA-antibody, and strengthens its potential role as a new surrogate marker for Hcrt-1 for targeted quantification. Hcrt-11-16 is significantly reduced in patients with narcolepsy type 1 and appears to serve as a possible marker to discriminate NT1 from controls using two different purification methods, prior to measurements by nano-liquid chromatography coupled to high resolution mass spectrometry. Findings will need replication in a larger and more diverse cohort, including patients with different central disorders of hypersomnolence and intermediate RIA measured hypocretin levels to further determine their clinical significance.

Indexed as

NarcolepsyOrexinsAdultBiomarkersChromatography, LiquidFemaleHumansMaleRadioimmunoassaySolid Phase ExtractionTandem Mass SpectrometryBiomarkersOrexinscerebrospinal fluidfragmenthypocretinmass spectrometrynarcolepsy type 1orexinquantificationradioimmunoassaysurrogate marker

Identifiers

PMID42139087
PMCPMC13658270

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.