{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:54:54Z","timestamp":1787032494832,"version":"build-2736575974"},"posted":{"date-parts":[[2026,1,2]]},"group-title":"Neurology","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder for which monitoring biomarkers are urgently needed. We aimed to evaluate whether proteins in serum can accurately monitor patients\u2019 function within the duration of a clinical trial.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this study, we evaluated longitudinal serum proteins of DMD patients participating to the FOR-DMD clinical trial, comparing daily and intermittent corticosteroid regimens in boys aged 4-8 years at baseline. Using the aptamer-based protein platform SomaScan, we profiled 1500 proteins. Associations between protein levels and motor function outcomes, such as Rise from the Floor Velocity (RFV), 10-Meter Run\/Walk Velocity (10MRWV), and North Star Ambulatory Assessment (NSAA), were assessed using linear mixed models. In particular, we explored whether patients with higher protein levels also tended to have better functional scores (across-patients analysis), and whether changes in protein levels within the same patient over time were linked to changes in their functional performance (within-patient analysis). Finally, penalized (Lasso) mixed models were applied to evaluate the predictive function of the proteins. The prediction accuracy of the models (evaluated by optimism-corrected Root Mean Squared Error) was compared to that of a simpler model with only age and treatment as predictors.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Across-patients and within-patient analyses revealed consistent associations with three functional tests for a subset of proteins, notably RGMA, ART3, ANTXR2, and CFB. Multivariate models incorporating the proteins significantly associated with at least two tests, improved prediction accuracy for NSAA and RFV by 21% and 8%, respectively. These models also revealed a subset of proteins that were consistently selected. Quantification of CFB, RGMA, ANTXR2, SERPINF1 and ATP5PF using SomaScan showed strong agreement with measurements obtained using orthogonal methods such as ELISA, MRM-MS and an in-house developed bead-based sandwich immunoassay.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>These findings support the utility of serum protein signatures as objective, quantitative tools for monitoring disease progression and treatment response in DMD during clinical visits and clinical trials.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.18.25342544","type":"posted-content","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T18:40:10Z","timestamp":1767379210000},"source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of a serum protein signature as monitoring biomarker for Duchenne Muscular Dystrophy in a long-term clinical trial with corticosteroids"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9993-9346","authenticated-orcid":false,"given":"Chiara","family":"Degan","sequence":"first","affiliation":[{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Tobin","sequence":"additional","affiliation":[{"name":"Carleton University, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon I.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Jim\u00e9nez-Requena","sequence":"additional","affiliation":[{"name":"Department of Protein Science, School of Chemistry, Biology and Health, KTH Royal Institute of Technology, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amela","family":"Peco","sequence":"additional","affiliation":[{"name":"Department of Protein Science, School of Chemistry, Biology and Health, KTH Royal Institute of Technology, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Guglieri","sequence":"additional","affiliation":[{"name":"The John Walton Muscular Dystrophy Research Center, Newcastle University, Newcastle Upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Diaz-Manera","sequence":"additional","affiliation":[{"name":"The John Walton Muscular Dystrophy Research Center, Newcastle University, Newcastle Upon Tyne, UK"},{"name":"Laboratori de Malalties Neuromusculars, Institut de Recerca de l\u2019Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en red en Enfermedades Raras (CIBERER), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri E. M.","family":"van der Burgt","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart J. M.","family":"Vlijmen","sequence":"additional","affiliation":[{"name":"Department of Hemostasis and Thrombosis, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"DMD investigators of the Muscle Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yetrib","family":"Hathout","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Binghamton, NY, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Al-Khalili Szigyarto","sequence":"additional","affiliation":[{"name":"Department of Protein Science, School of Chemistry, Biology and Health, KTH Royal Institute of Technology, Stockholm, Sweden"},{"name":"Science for Life Laboratory, Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utkarsh J.","family":"Dang","sequence":"additional","affiliation":[{"name":"Carleton University, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roula","family":"Tsonaka","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2783-688X","authenticated-orcid":false,"given":"Pietro","family":"Spitali","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, the 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