Circulating protein biomarkers identified in two independent clinical trial cohorts of glucocorticoid-naive Duchenne muscular dystrophy patients.

Blood-accessible biomarkers offer promising insights into the pathogenesis of Duchenne muscular dystrophy (DMD) and other muscle diseases. Here, we quantified the relative abundance of 7,289 serum proteins using SomaScan proteomics in pre-treatment samples from 51 boys with DMD (aged 4 to <7) and 13 healthy controls from the VISION DMD (VBP15-004) trial. An independent validation cohort of untreated DMD boys (aged 4 to <8) from the FOR-DMD trial was also analyzed. Of the proteins screened, 26% and 15% were significantly elevated and decreased, respectively, in the serum of young DMD boys compared to controls (adjusted p-value < 0.05). A high correlation (Spearman r = 0.85) in fold changes was observed between the two datasets. Many proteins with altered levels overlapped with known markers of muscle injury, inflammation, regeneration, and extracellular matrix remodeling. Selected biomarkers were queried in two published muscle mRNA and a muscle snRNAseq dataset in DMD biopsies. Novel factors involved in muscle regeneration and ECM remodeling were identified. This larger-scale, multi-clinical trial-based cohort study in untreated DMD boys substantially expands the catalog of circulating biomarkers, highlighting early-stage pathological processes. These findings can help identify new therapeutic targets and develop clinically actionable biomarkers to assess disease progression and response to therapies.

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Journal
Scientific Reports
Published
2025-11-14
DOI
https://doi.org/10.1038/s41598-025-23758-6
Citations
1
Primary Topic
Muscle Physiology and Disorders
Type
article
Field-Weighted Citation Impact
0.81

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article

Circulating protein biomarkers identified in two independent clinical trial cohorts of glucocorticoid-naive Duchenne muscular dystrophy patients.

Gian Luca Vita, Kathleen O’Reardon, Rabi Tawil, Miriana d’Alessandro et al.
1 citations
Scientific Reports
Muscle Physiology and Disorders
0.81
article

Circulating protein biomarkers identified in two independent clinical trial cohorts of glucocorticoid-naive Duchenne muscular dystrophy patients.

Gian Luca Vita, Kathleen O’Reardon, Rabi Tawil, Miriana d’Alessandro, Elaine McColl, Yuri E. M. van der Burgt, W. Bryan Burnette, Migvis Monduy, Elena Pegoraro, E. Niks, Ekkehard Wilichowski, Mary W. Brown, Robert C. Griggs, N. Kuntz, Cristina Al‐Khalili Szigyarto, Michela Guglieri, Marina Katsalouli, Stefan Spinty, Ashutosh Kumar, Janbernd Kirschner, Giuseppe Vita, Monique M. Ryan, Rebecca Tobin, Nancy L. Kuntz, Leslie Morrison, Tina Duong, Richard Webster, Nanette C. Joyce, Carolina Tesi Rocha, Jay J. Han, Z. Alhaswani, Henriette van Ruiten, Vamshi K. Rao, Albert Jiménez-Requena, Erik Henricson, Tiziana Mongini, Federica Ricci, Imelda Hughes, Kathryn A. Selby, Annie M. Sbrocchi, Erica Goude, Anjum Naveed, Utkarsh J. Dang, Ulrike Schara‐Schmidt, Jesse M. Damsker, Yoram Nevo, Liesbeth De Waele, L. Mengle-Gaw, Emma Ciafaloni, Iain Horrocks, Nathalie Goemans, M. Tulinius, Richard J. Barohn, Stefanie de Vries, Michele Yang, Kevin M. Flanigan, Roula Tsonaka, Lauren P. Morgenroth, Craig Campbell, Helen Roper, Jennifer Wilkinson, P. Morehart, Maja von der Hagen, C. Degan, Luca Bello, Peter B. Kang, Russell J. Butterfield, IA Horrocks, Jeffrey Statland, Pietro Spitali, Andres Nascimento-Osorio, Seth J. Perlman, Chris Speed, Diana Castro, Craig M. McDonald, Edward C. Smith, Benjamin D. Schwartz, Jordi Díaz‐Manera, Leanne Marie Ward, Lorenzo Maggi, Basil T. Darras, Nicolas Deconinck, Juan J. Vílchez, Yetrib Hathout, Perry B. Shieh, Taeun Chang, Richard S. Finkel, Tracey Willis, Hugh J. McMillan, Eric P. Hoffman, Monika Krzesniak‐Swinarska, Matthew Wicklund, Paula R. Clemens, William B. Martens, Fatemeh Ahmadi-Harchegani, Michael P. McDermott, Imelda JM De Groot, Mathula Thangarajh, Giovanni Baranello, Adnan Manzur, Kate Bushby, Barbara E. Herr, Anne-Marie Childs, Jana Haberlová, Wendy King, Michelle Eagle, Amy Harper, Mika Leinonen, John N. Van DenAnker, James FHoward, Andrea Gangfus
article en
1 citations

Abstract

Blood-accessible biomarkers offer promising insights into the pathogenesis of Duchenne muscular dystrophy (DMD) and other muscle diseases. Here, we quantified the relative abundance of 7,289 serum proteins using SomaScan proteomics in pre-treatment samples from 51 boys with DMD (aged 4 to <7) and 13 healthy controls from the VISION DMD (VBP15-004) trial. An independent validation cohort of untreated DMD boys (aged 4 to <8) from the FOR-DMD trial was also analyzed. Of the proteins screened, 26% and 15% were significantly elevated and decreased, respectively, in the serum of young DMD boys compared to controls (adjusted p-value < 0.05). A high correlation (Spearman r = 0.85) in fold changes was observed between the two datasets. Many proteins with altered levels overlapped with known markers of muscle injury, inflammation, regeneration, and extracellular matrix remodeling. Selected biomarkers were queried in two published muscle mRNA and a muscle snRNAseq dataset in DMD biopsies. Novel factors involved in muscle regeneration and ECM remodeling were identified. This larger-scale, multi-clinical trial-based cohort study in untreated DMD boys substantially expands the catalog of circulating biomarkers, highlighting early-stage pathological processes. These findings can help identify new therapeutic targets and develop clinically actionable biomarkers to assess disease progression and response to therapies.

Scientific ReportsVol. 15(1)
University of Messina (IT), University of North Carolina at Chapel Hill (US), Binghamton University (US), Western University (CA), Boston Children's Hospital (US), Lurie Children's Hospital (US), Leeds General Infirmary (GB), Western Pennsylvania School for Blind Children (US), Hospital Sant Joan de Déu Barcelona (ES), University Hospitals Birmingham NHS Foundation Trust (GB), St. Jude Children's Research Hospital (US), Nationwide Children's Hospital (US), Royal Children's Hospital (AU), Children's National (US), Harvard University (US), University of Padua (IT), Radboud University Nijmegen (NL), University of Ottawa (CA), University of California, Los Angeles (US), Tel Aviv University (IL), University of Calgary (CA), University of New Mexico (US), University of Pittsburgh (US), Duke University (US), Virginia Commonwealth University (US), George Washington University (US), University of Washington (US), University of Missouri–St. Louis (US), Charles University (CZ), University of Utah (US), Children's Hospital of Eastern Ontario (CA), Leeds Teaching Hospitals NHS Trust (GB), University Hospital Bonn (DE), Montreal Children's Hospital (CA), Leiden University Medical Center (NL), Great Ormond Street Hospital (GB), NHS Greater Glasgow and Clyde (GB), Royal Hospital for Children (GB), University Medical Center Freiburg (DE), UCLA Medical Center (US), Alberta Children's Hospital (CA), Children's Hospital at Westmead (AU), Robert Jones and Agnes Hunt Orthopaedic Hospital (GB), Radboud University Medical Center (NL), University of California System (US), University of Rochester Medical Center (US), Ghent University (BE), Alder Hey Children's NHS Foundation Trust (GB), Children's Hospital Colorado (US), Santhera Pharmaceuticals (Switzerland) (CH), Southwestern Medical Center (US), University Hospital in Motol (CZ), Drottning Silvias barn- och ungdomssjukhus (SE), Schneider Children's Medical Center (IL), Hospital Quirónsalud Barcelona (ES), Universitätsmedizin Göttingen (DE), Essen University Hospital (DE), University of Kansas Medical Center (US), ReveraGen BioPharma (United States) (US), University of Pittsburgh Medical Center (US), University of Minnesota Medical Center (US), UCL Biomedical Research Centre (GB), Miami Children's Hospital (US), Murdoch Children's Research Institute (AU), BC Children's Hospital (CA), Nemours Children's Clinic (US), NIHR Research Delivery Network (GB), Panagiotis & Aglaia Kyriakou Children's Hospital (GR), Royal Manchester Children's Hospital (GB), University Hospital Carl Gustav Carus (DE), Centro Neurolesi Bonino Pulejo (IT), Fondazione IRCCS Istituto Neurologico Carlo Besta (IT), Children's Hospital of Richmond at VCU (US), Southwestern Medical Center (US), Alberta Children's Hospital Research Institute, University College London (GB), University of Colorado Anschutz Medical Campus (US), The Ohio State University (US), University of Turin (IT), Carleton University (CA), University of Missouri (US), Technische Universität Dresden (DE), Penn State Milton S. Hershey Medical Center (US), University of California, Davis (US), Newcastle University (GB), The University of Texas Southwestern Medical Center (US), KTH Royal Institute of Technology (SE), Vanderbilt University Medical Center (US), University of Colorado Denver (US), Stanford University (US), KU Leuven (BE)
U.S. Department of Defense, Foundation to Eradicate Duchenne, National Institutes of Health, National Institute of Neurological Disorders and Stroke
Openalex Percentile: Top 22%
Muscle Physiology and Disorders
0.81
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