Tau and Beyond: Proteomic Profiling of Neurodegenerative Diseases with a 120-Plex CNS Disease Panel

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Abstract

The global rise of an increasingly aging population has heightened the need for biomarkers for the early detection of aging-related diseases including neurodegenerative diseases (NDD). Fluid-based biomarkers, especially blood-based biomarkers that can be detected in a minimally invasive manner, are highly valuable. However, progress in translational research has been impeded by a lack of highly multiplexed and ultrasensitive proteomic technologies. Addressing this challenge, we developed NULISA™, which employs DNA-conjugated antibodies to convert immunocomplexes into reporter DNA molecules that can be analyzed with real-time PCR (qPCR) or next-generation sequencing (NGS) to achieve attomolar limit of detection (low to sub-fg/mL) and 100s-plex capability. Here we report the development of a 120-plex NULISA panel – CNS Disease Panel 120 – for comprehensive profiling of NDD. This panel includes well-established biomarkers such as neurofilament light, alpha-synuclein and multiple phosphorylated Tau proteoforms (p-Tau181, p-Tau217 and p-Tau231) as well as other proteins implicated in NDD. We evaluated the performance of this assay with blood (n=38) and cerebrospinal fluid (CSF) (n=29) samples from healthy controls and NDD patients. With just 10 mL plasma or CSF, NULISA demonstrated high sensitivity (~95% detectability in plasma and ~80% in CSF) and high precision (median CV ~6.0%). Linear model analysis identified both known and novel proteins with significant differences between disease and age-matched controls. With full automation in a high throughput system (ARGO HT™), NULISA CNS Disease Panel 120 holds great promise to reveal new biological insights into aging and disease mechanisms and enable biomarker discovery through large cohort and population-based studies.

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.