Abstract Details

Title How Robust Are Biomarkers for the Huntington Disease Continuum?

Topic Movement Disorders

Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-012

Objective This systematic review aims to quantify Huntington’s disease (HD) biofluid biomarkers by their effects sizes to distinguish HD from healthy controls and evaluate their quality and level of evidence.

Background Sensitive and specific biomarkers are needed to monitor disease progression and treatment response in HD. However, studies have been limited by sample size and design heterogeneity.

Design/Methods A systematic literature review in PubMed from 2/18/17 to 7/24/23 was performed to review literature regarding candidate saliva, urine, blood, and cerebrospinal fluid biomarkers for HD. Study selection and assessment of quality were conducted by three independent reviewers. The search yielded 621 results, 191 of which met review inclusion criteria. Study-specific sample sizes, means, and standard deviations were extracted from all identified publications and assessed via the standardized mean difference between HD and healthy controls. Standardized mean differences were estimated by Hedges’ g.

Results A majority of publications failed to report sufficient summary statistics for a comparison across studies to be conducted. Only 24 of 621 publications met analysis inclusion criteria. We focused on biomarkers that have been validated in at least two independent cohorts. The following biomarkers showed potential for distinguishing between healthy controls and stages of HD: BDNF; IL-6; NfL; T-tau; tHtt; YKL-40. Effect sizes for mHTT were included even though it was only represented in one article.

Conclusions Numerous published biomarkers encompass inflammatory, metabolic, and oxidative stress pathways, with emphasis on markers of neuronal degeneration. Neurofilament light chain is the most consistent biomarker in the literature in addition to BDNF, IL-6, T-tau, tHtt, and YKL-40, which show the most robust differentiation between healthy controls and the stages of HD. Unfortunately, publication bias in biomarker research is widespread given (1) the lack of reporting regarding non-significant findings and (2) the absence of information necessary to sufficiently evaluate potential biomarkers for qualification and context of use.

Authors/Disclosures
Maria Rudrud PRESENTER	No disclosure on file
Jane S. Paulsen, PhD (University of Wisconsin, Madison)	Dr. Paulsen has received personal compensation in the range of $0-$499 for serving as a Consultant for CHDI. Dr. Paulsen has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Wave Life Sciences. Dr. Paulsen has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for HDSA. The institution of Dr. Paulsen has received research support from NIH/NIA. The institution of Dr. Paulsen has received research support from NIH/NINDS.
Alex Pinto (UW Madison)	No disclosure on file
Natalie Bovin	No disclosure on file
Esha Mahalingam	No disclosure on file
Monica L. Janz, MD	Miss Janz has nothing to disclose.
William Adams	No disclosure on file
Michael Newton	No disclosure on file
Henry J. Bockholt (Georgia State University)	The institution of Henry Bockholt has received research support from NIH. The institution of an immediate family member of Henry Bockholt has received research support from NIH.
Kathleen M. Shannon, MD, FAAN (University of Wisconsin School of Medicine and Public Health)	The institution of Dr. Shannon has received research support from Inhibikase Therapeutics. The institution of Dr. Shannon has received research support from ASKBIO. Dr. Shannon has received personal compensation in the range of $500-$4,999 for serving as a Grant reviewer with NIH.

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