ArticleAnnals of clinical and translational neurology2026
Discovery and Targeted Proteomic Studies Reveal Striatal Markers Validated for Huntington's Disease.
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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The trial behind it
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Neurobiological Predictors of Huntington's Disease Trial
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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.
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