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Cell HGG Advances

Targeted plasma proteomics uncover novel proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders

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  • August 26, 2025
  • Depesh Pant, et al.,  Emory University School of Medicine
Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
ALS
Sample Type:
Plasma

Abstract

KIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a novel multiplex NULISA targeted platform to analyze plasma proteome from KIF5A-linked SPG10, ALS patients and compared to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function, and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG10 patients. Moreover, these findings can now be taken forward to gain mechanistic understanding of axonopathies linking to N-vs C-terminal KIF5A variants affecting both central and peripheral nervous systems.

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Authors & Affiliations

Jarosław Dulski, M.D., Ph.D.1,2,3, Arun K. Boddapati, M.S.4, Barbara Risi, M.D.5,6, Pablo Iruzubieta, M.D., Ph.D.7, Antonio Orlacchio, M.D., Ph.D.8,9, Roberto Fernández-Torrón, M.D.7, Tamara Castillo-Triviño, M.D.7, Adolfo López de Munain, M.D., Ph.D.7, Steve Vucic, M.D., Ph.D.10, Laura Donker Kaat, M.D., Ph.D.11, Tahsin Stefan Barakat, M.D., Ph.D.11, Leonard Petrucelli, Ph.D.12, Mercedes Prudencio, Ph.D.12, John E. Landers, Ph.D.13, Jochen H. Weishaupt, M.D.14, Andreas Prokop, Ph.D.15, Massimiliano Filosto, M.D., Ph.D.5,16, Zbigniew K. Wszolek, M.D.3*, Devesh C. Pant, Ph.D.17*

  1. Division of Neurological and Psychiatric Nursing, Medical University of Gdańsk, Poland
  2. Neurology Department, St Adalbert Hospital, Copernicus PL Ltd., Gdansk, Poland
  3. Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
  4. Independent Scholar N Druid, Decatur, GA, USA
  5. NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy
  6. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
  7. Neurology Department, Donostia University Hospital, Osakidetza, and Biodonostia Health Research Institute-UPV-EHU, San Sebastián, Spain
  8. Department of Medicine and Surgery, University of Perugia, Perugia, Italy
  9. Hospital Company of Perugia – “Santa Maria della Misericordia” Hospital, Perugia, Italy
  10. Brain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, Australia
  11. Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, Netherlands
  12. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
  13. Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA
  14. Department of Neurology, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany
  15. The University of Manchester, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, School of Biology, Manchester, UK
  16. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
  17. Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA
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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.

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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.