Cerebrospinal Fluid Myeloperoxidase Is Associated With Putamen Volume Beyond Neurofilament Light in Huntington’s Disease

Product:

CNS Disease Panel 120, Inflammation Panel 250

Topic:

Neurology

Disease Area:

Huntington's Disease

Sample Type:

CSF

Abstract

Background The primary neuroanatomical site of Huntington’s disease (HD) pathology resides in the striatum and its atrophy identifies important disease progression from HD-ISS Stage 0 to Stage 1. Immune-associated proteins may capture variation in HD that is incompletely represented by markers of neuroaxonal injury.

Objectives To determine whether cerebrospinal-fluid myeloperoxidase contributes information about striatal volume loss beyond genetic disease burden and neurofilament light.

Methods Cross-sectional data from 88 persons with HD were analyzed. Cerebrospinal-fluid myeloperoxidase and neurofilament light were measured with a nucleic acid-linked immunosandwich assay. Normalized putamen volume was derived from structural magnetic resonance imaging. Linear regression adjusted for genetic disease burden and sex.

Results Higher neurofilament light was associated with smaller normalized putamen volume (standardized β = −0.322, (P=.0066)). Higher myeloperoxidase was associated with larger normalized putamen volume after adjustment for genetic disease burden, sex, and neurofilament light (standardized β = 0.183, (P=.0386)). Adding myeloperoxidase increased explained variance in striatal loss.

Conclusions Cerebrospinal fluid myeloperoxidase contributed modest incremental information about striatal volume in this cross-sectional sample. Independent longitudinal studies are needed to determine its biological source, temporal behavior, and potential biomarker value. Findings advance efforts to characterize multicomponent biological markers of HD.

READ THE PRE-PRINT

Authors and Affiliations

Jordan D. Clemsen, BA¹, H. Jeremy Bockholt, MS¹˒², William H. Adams³, Bradley T. Baker, PhD¹, Jessica L. Bolton, PhD⁴, Vince D. Calhoun, PhD¹, and Jane S. Paulsen, PhD²*

¹ Tri-Institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State University, Georgia Institute of Technology, Emory University
² University of Wisconsin–Madison
³ Loyola University Chicago
⁴ Georgia State University

* Corresponding author: Jane S. Paulsen

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition. He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.