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Publication
medRxiv

Identification of a presymptomatic and early disease signature for Amyotrophic Lateral Sclerosis (ALS): protocol of the premodiALS study

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  • May 27, 2025
  • Paul Lingor, et al., DZNE
Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
ALS
Sample Type:

Abstract

The median time to diagnosis of amyotrophic lateral sclerosis (ALS) is approximately 12 months after the onset of first symptoms. This diagnostic delay is primarily due to the nonspecific nature of early symptoms and the clinical challenges in differentiating ALS from its mimics. Therefore, the discovery of reliable biomarkers for the early and accurate diagnosis of ALS represents a critical medical need. A total of 330 participants will be recruited across six international study sites. The cohort will include (1) pre-symptomatic gene mutation carriers, (2) symptomatic individuals up to 12 months after symptom onset with either ALS, ALS mimics, or a pure motor syndrome with yet unclear assignment, and (3) healthy controls. Participants will engage in a one-year longitudinal study, consisting of an initial evaluation at baseline visit and a follow-up visit 12 months later. Assessments will include an environmental and medical history questionnaire, neurological examinations, olfactory testing, cognitive/behavioral evaluations, and the collection of biological samples (serum, plasma, urine, tear fluid, and cerebrospinal fluid). Proteomic, metabolomic, and lipidomic analyses will be performed using mass spectrometry and targeted immunoassays, with all samples processed under standardized protocols. The resulting multimodal dataset will be systematically integrated in an effort to uncover a clinico-molecular signature characteristic of presymptomatic and early ALS. These findings may have relevance to early ALS diagnosis and future clinical practice.

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Authors & Affiliations

Laura Tzeplaeff1*, Ana Galhoz2,3, Clara Meijs2, Lucas Caldi Gomes1, Andrej Kovac4, Amrei Menzel5, Hatice De ğ irmenci6, Abir Alaamel6, Hüseyin Can Kaya6, Ali Günalp Çelik6, Sine Dinçer6, Meltem Korucuk7, Sibel Berker Karaüzüm6, Elif Bayraktar8, Vildan Çiftçi8, U ğ ur Bilge6, Filiz Koç9, Antonia F Demleitner1, Anne Buchberger1, Ricarda von Heynitz1, Vincent Gmeiner1, Christina Knellwolf10, Mohammed Mouzouri11, Joanne Wuu12, A. Nazlı Ba ş ak8, Peter Munch Andersen13, Florian Kohlmayer5, Nicholas J Ashton14,15,16, Wojciech Kuban17, Christof Lenz18,19, Mary-Louise Rogers20, Norbert Zilka4, Philippe Corcia11, Yossef Lerner21, Markus Weber10, Monika Turcanova Koprusakova22, Hilmi Uysal6, Michael Benatar12, Michael P Menden2,23 and Paul Lingor1,24,25 1 2 3 4 5 6 7 8 9

  1. Department of Neurology, Rechts der Isar Hospital of the Technical University Munich, Munich (Germany).
  2. Department of Computational Health, Helmholtz Munich, Neuherberg (Germany).
  3. Department of Biology, Ludwig-Maximilians University Munich, Munich (Germany).
  4. Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava (Slovakia).
  5. Bitcare GmbH, Technical University of Munich, Munich (Germany).
  6. Department of Neurology, Akdeniz University Hospital, Antalya (Türkiye).
  7. Neuromuscular Center, Antalya Education and Research Hospital, Antalya (Türkiye).
  8. Koç University, School of Medicine, Research Center for Translational Medicine KUTTAM, Neurodegeneration Research Laboratory NDAL, Istanbul (Türkiye).
  9. Neurology Department, Çukurova University, Adana (Türkiye).
  10. Neuromuscular Diseases Center/ALS Clinic of the Kantonsspital St. Gallen, St. Gallen (Switzerland).
  11. Centre de Reference SLA et autres maladies du neurone moteur, Department of Neurology, CHRU Bretonneau, Tours (France).
  12. Department of Neurology and ALS Center, University of Miami Miller School of Medicine, Miami, Florida (USA).
  13. Department of Clinical Science, Neurosciences, Umeå University, Umeå (Sweden).
  14. Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg (Sweden).
  15. Banner Alzheimer’s Institute and University of Arizona, Phoenix, Arizona (USA).
  16. Banner Sun Health Research Institute, Sun City, Arizona (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.