UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Lack of evidence for kynurenine pathway dysfunction in Huntington's disease: Cerebrospinal fluid and plasma analyses from the HDClarity study

Khetarpal, Vinod; Herbst, Todd; Dominguez, Celia; Munoz-Sanjuan, Ignacio; Sampaio, Cristina; Marks, Bryan; Miller, Dennis L; ... Pacifici, Robert; + view all (2025) Lack of evidence for kynurenine pathway dysfunction in Huntington's disease: Cerebrospinal fluid and plasma analyses from the HDClarity study. Journal of Huntington's Disease 10.1177/18796397241301761. (In press). Green open access

[thumbnail of Wild_KP Metabolites Manuscript Revised Final 5th Nov 2024.pdf]
Preview
Text
Wild_KP Metabolites Manuscript Revised Final 5th Nov 2024.pdf

Download (1MB) | Preview

Abstract

BACKGROUND: Evidence from animal studies and post-mortem studies of brains from people with Huntington's disease (PwHD) has suggested that the kynurenine pathway (KP) may be dysregulated in Huntington's disease (HD). OBJECTIVE: To determine whether there are differences in KP metabolites in the cerebrospinal fluid (CSF) and plasma of PwHD vs. healthy controls enrolled in the HDClarity study. METHODS: CSF and plasma samples from 141 PwHD with mild and moderate manifest disease and 75 healthy controls were analyzed for 3-hydroxykynurenine (3-OH-KYN), quinolinic acid, kynurenine, anthranilic acid, kynurenic acid, and tryptophan concentrations using validated high-performance liquid chromatography with tandem mass spectrometry methods. The primary and secondary endpoints compared metabolite concentrations between groups, and an exploratory analysis (PwHD only) evaluated the association between the metabolite levels and severity of disease. RESULTS: No significant differences in CSF or plasma concentrations of any of the six KP metabolites were observed between PwHD and controls, and there were no strong associations between the concentration of any KP metabolite and disease severity. A principal component analysis of the combined CSF and plasma measures showed a substantial positive correlation among all metabolites except for tryptophan in plasma. CONCLUSIONS: We found no evidence to support the hypothesis of dysregulation of KP metabolites in HD based on CSF and plasma metabolite levels. The monitoring of KP metabolites in CSF or plasma is unlikely to serve as a pharmacodynamic biomarker for disease progression or therapeutic intervention in HD.

Type: Article
Title: Lack of evidence for kynurenine pathway dysfunction in Huntington's disease: Cerebrospinal fluid and plasma analyses from the HDClarity study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/18796397241301761
Publisher version: https://doi.org/10.1177/18796397241301761
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10204646
Downloads since deposit
5Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item