Biomarker discovery using NUcleic Acid-Linked Immuno-Sandwich Assay in multiple sclerosis patients experiencing progression independent of relapse activity

Topic/Product:
CNS Disease Panel 120, Inflammation Panel 250, Neurology
Disease Area:
Multiple Sclerosis (MS)
Sample Type:
Plasma

Abstract

Background/Objectives:

This cohort study aimed to identify blood-based biomarkers associated with progression independent of relapse activity (PIRA) in persons with multiple sclerosis (pwMS) using the multiplex NUcleic Acid-Linked Immuno-Sandwich Assay (NULISA).

Methods:

NULISA ‘CNS Disease Panel’ and ‘Inflammation Panel’ were applied on plasma samples from pwMS following B cell-depleting therapy (BCDT; n = 185) or fingolimod (n = 200), median follow-up 4.0 (BCDT) and 9.1 (fingolimod) years. Plasma NULISA results (322 unique proteins; 0.9 and 1 year after treatment start, respectively) were investigated for their potential to prognosticate PIRA.

Results:

‘CNS Disease Panel’ derived glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were identified as predictive of PIRA by multivariable Cox regression models (GFAP: BCDT: hazard ratio (HR) = 1.79, 95% confidence interval (CI) = 1.26–2.55, p = 0.0011; fingolimod: HR = 1.73, 95% CI = 1.14–2.64, p = 0.0104; NfL: BCDT: HR = 1.99, 95% CI = 1.31–3.02, p = 0.0013). GFAP derived from the ‘Inflammation Panel’ exhibited patterns like those observed with ‘CNS Disease Panel’ derived GFAP. Beyond GFAP and NfL, 12 biomarker candidates predictive of PIRA were identified. No target passed multiple test corrections, but GFAP consistently showed the highest hazard.

Conclusion:

Among over 300 proteins investigated by NULISA, GFAP was the main biomarker significantly associated with future PIRA risk in our cohort.

Authors & Affiliations

Sofia Sandgren, Aleksandra Maleska Maceski, Pascal Benkert, Maximilian Einsiedler , Sabine Schaedelin, Johanna Oechtering, Lutz Achtnichts, Patrice H Lalive, Stefanie Müller, Caroline Pot , Amanda Heslegrave, David Hunt, Jan Lycke , Robert Hoepner, Patrick Roth, Claudio Gobbi , Manuel Comabella , Tobias Derfuss , Ludwig Kappos  Cristina Granziera , Ahmed Abdelhak , David Leppert, Eline AJ Willemse, Henrik Zetterberg and Jens Kuhle

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.