Evidence mapPaperPMID 41363816Full record

ArticleAnnals of clinical and translational neurology2026

Discovery and Targeted Proteomic Studies Reveal Striatal Markers Validated for Huntington's Disease.

Daniel Chelsky, Cara Joyce, H Jeremy Bockholt, Paul A Rudnick, William H Adams, Fiona McAllister, Justin W Smock, Michael A Newton, Jane S Paulsen

Registry-linked trialAbstract read
In one paragraph

Article in Annals of clinical and translational neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00051324 (Neurobiological Predictors of Huntington's Disease Trial), which is not on this 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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00051324 active not recruitingnot on this map

Neurobiological Predictors of Huntington's Disease Trial

TypeobservationalSponsorJordan SchultzRan2002 to 2025Enrolled1,700ConditionsHuntington Disease
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Daniel ChelskyCellCarta, Inc., Montreal, Quebec, Canada.
Cara JoyceDepartment of Biostatistics, Center for Translational Research and Education, Loyola University Chicago, Maywood, Illinois, USA.
H Jeremy BockholtTri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, Georgia, USA.
Paul A RudnickSpectragen Informatics, LLC, Bainbridge Island, Washington, USA.
William H AdamsDepartment of Biostatistics, Center for Translational Research and Education, Loyola University Chicago, Maywood, Illinois, USA.
Fiona McAllisterCellCarta, Inc., Montreal, Quebec, Canada.
Justin W SmockDepartment of Internal Medicine, University of Iowa, Iowa, USA.
Michael A NewtonDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jane S PaulsenDepartment of Neurology, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0000-0002-0983-228X

Funding

Preparing for preventive clinical trials in Huntington's diseaseU01NS105509 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · 2024 to 2025
$1.5M
NIH HHS NS040068NIH HHS NS082089NIH HHS NS103475NIH HHS NS105509NINDS NIH HHS R01 NS105509NINDS NIH HHS U01 NS105509
6 · The paper itself

Abstract

objectiveClinical trials for Huntington's disease (HD) enrolling persons before clinical motor diagnosis (CMD) lack validated biomarkers. This study aimed to conduct an unbiased discovery analysis and a targeted examination of proteomic biomarkers scrutinized by clinical validation.

methodsCerebrospinal fluid was obtained from PREDICT-HD and ancillary studies. Cohorts included HD family members who were gene-tested and considered prodromal following neuroexam. An initial unbiased mass spectrometry proteomics analysis identified candidate disease biomarkers that were then added to a targeted mass spectrometry assay including 100+ proteins associated with other neurodegenerative diseases. This assay determined relative quantifications of proteins in a single analysis. Significant biomarkers were examined against genetic and clinical measures of disease onset and progression.

resultsTwo overlapping targeted analyses using 180 samples from 125 participants (61% female, 89% White, average age of 42 ± 14) were performed; longitudinal duration was 1-4 years. Based on participants' clinical data, 25 proteins correlated significantly with CAG-age-product (CAP) score and Unified HD Rating Scale (UHDRS) motor and cognitive measures. While most proteins increase in abundance with disease progression, proenkephalin and prodynorphin were downregulated before CMD. Power was low for longitudinal analysis. However, the reliability of HD family normal controls indicates that each individual's proteome remains relatively stable over time.

interpretationFindings replicate and extend the verification of HD biomarkers. Monitoring proenkephalin and prodynorphin levels in persons with HD may facilitate early detection and disease-tracking. These disease-specific biomarkers may improve the rigor of therapeutic intervention before clinical motor diagnosis. Further studies emphasizing longitudinal changes are needed to assess disease-monitoring.

trial registrationClinicalTrials.gov identifier: NCT00051324.

Indexed as

Corpus StriatumEnkephalinsHuntington DiseaseProtein PrecursorsProteomicsAdultBiomarkersDisease ProgressionFemaleHumansMaleMiddle AgedBiomarkersEnkephalinsproenkephalinProtein PrecursorsbiomarkersHuntington's diseaseproteomicsqualificationstriatum

Identifiers

PMID41363816
PMCPMC13161869

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Registered trials

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 Socratic graph.