Identifying novel response markers for spinal muscular atrophy revealed by targeted proteomics following gene therapy

Product:

CNS Disease Panel 120

Topic:

Gene Therapy

Disease Area:

Spinal Muscular Atrophy (SMA)

Sample Type:

Plasma

Topic/Product:

CNS Disease Panel 120

Disease Area:

Spinal Muscular Atrophy (SMA)

Sample Type:

Plasma

Abstract

Spinal muscular atrophy (SMA) is a progressive disease that affects motor neurons, with symptoms usually starting in infancy or early childhood. Recent breakthroughs in treatments targeting SMA have improved both lifespan and quality of life for infants and children with the disease. Given the impact of these treatments, it is essential to develop methods for managing treatment-induced changes in disease characteristics. Zolgensma® is the first effective and approved gene therapy for SMA caused by biallelic mutation in the SMN1 gene. In three children with SMA treated with Zolgensma®, neuronal, glial, inflammation, and vascular markers in the plasma exhibited a quicker response, emphasizing their potential as valuable biomarkers of treatment efficacy in clinical trials. We chose the novel Nucleic acid Linked Immuno-Sandwich Assay, to investigate a predefined panel of neuroinflammatory markers in plasma samples collected from SMA patients at baseline and six months after Zolgensma® treatment. We identified a set of novel targets whose levels differed between pre and post Zolgensma® treatment group and that were responsive to treatment. Even though our results warrant validation in larger SMA cohorts and longer follow-up time, they may pave the way for a panel of responsive proteins solidifying biomarker endpoints in SMA clinical trials.

Authors & Affiliations

Devesh C. Pant & Sumit Verma, Emory University.

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.