Publications

Development of NULISAseq™ CNS Disease Panel 120 for Comprehensive Proteomic Profiling of Neurodegenerative Diseases

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Abstract

Background:

The development of reliable blood biomarkers for neurodegenerative diseases (NDDs) has been hindered by the lack of tools with sufficient sensitivity to detect low concentrations of brain-derived proteins in plasma or serum in a highly multiplexed manner. NULISA™ (NUcleic acid-Linked Immuno-Sandwich Assay) has emerged as a promising solution, with attomolar sensitivity and capable of high multiplexing in a fully automated system. In this study, we introduce NULISAseq™ CNS Disease Panel 120, a 120-plex NULISAseq assay for profiling key hallmarks of NDDs in both blood and cerebrospinal fluid (CSF).

Methods: NULISAseq CNS Disease Panel 120 includes many established and emerging disease markers such as amyloid beta 38/40/42, phosphorylated Tau (p-Tau181, p-Tau217, and p-Tau231), neurofilament light and alpha synuclein as well as APOE ε4 for APOE status. NULISA single-plex assays for each target were developed and pooled into a 120-plex assay with signal tuning to optimize detection of both low and high abundance targets simultaneously in both plasma and CSF samples. Performance assessment included target detectability, assay precision, and detection of differential abundance between disease and control groups using plasma (n=40) and CSF (n=16) samples from NDD patients and age-matched controls.

Results: We developed a CNS disease panel consisting of 120 targets linked to various pathways and processes characteristic of NDDs. Using just 10 µL of plasma or CSF, NULISAseq CNS Disease Panel 120 detected approximately 95% of targets in plasma and around 85% in CSF. It demonstrated high precision, with a median coefficient of variation (CV) of approximately 6.0%. Through linear regression analysis, we identified both known and novel proteins exhibiting significant differences in abundance between disease and age-matched controls. Furthermore, the APOE ε4 assay accurately classified donor APOE status into carriers and non-carriers using both sample types.

Conclusion: We developed a comprehensive CNS disease-targeted panel for the NULISA platform to meet the increasing demand for blood-based biomarker discovery and validation. NULISAseq CNS Disease Panel 120 provides a powerful new research tool for the early detection and diagnosis of NDDs and developing novel therapeutic interventions.

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.