Fatemeh Ahmadi-Harchegani, Rebecca Tobin, C. Degan, Ahmed Naveed, Michela Guglieri, Albert Jiménez-Requena, Sharon I. de Vries, Cristina Al‐Khalili Szigyarto, Pietro Spitali, Roula Tsonaka, Yuri E. M. van der Burgt, Jordi Díaz‐Manera, VBP15-004 investigators, CINRG DNHS investigators, Jesse M. Damsker, Seth J. Perlman, Edward C. Smith, Iain Horrocks, Richard S. Finkel, Jean K. Mah, Nicolas Deconinck, Nathalie Goemans, Jana Haberlová, Volker Straub, L. Mengle-Gaw, Benjamin D. Schwartz, Amy Harper, Perry B. Shieh, Liesbeth De Waele, Diana Castro, Michele Yang, Monique M. Ryan, Craig M. McDonald, Erik Henricson, Erica Goude, M. Tulinius, Richard Webster, Hugh J. McMillan, N. Kuntz, Vamshi K. Rao, Giovanni Baranello, Stefan Spinty, Anne-Marie Childs, Annie M. Sbrocchi, Kathryn Selby, Migvis Monduy, Yoram Nevo, Juan J. Vílchez, Andres Nascimento-Osorio, E. Niks, Imelda JM De Groot, Marina Katsalouli, John N. Van DenAnker, Leanne M. Ward, Mika Leinonen, Tina Duong, Carolina Tesi Rocha, Mathula Thangarajh, MD Andrea L. D’Alessandro, Lauren P. Morgenroth, FOR-DMD investigators of the Muscle Study Group, Kate Bushby, Michael P. McDermott, P. Morehart, Rabi Tawil, William B. Martens, Barbara E. Herr, Elaine McColl, Chris Speed, Jennifer Wilkinson, Janbernd Kirschner, Wendy King, Michelle Eagle, Mary W. Brown, Tracey Willis, Robert C. Griggs, Volker Straub, Henriette van Ruiten, Anne-Marie Childs, Emma Ciafaloni, Perry B. Shieh, Stefan Spinty, Lorenzo Maggi, Giovanni Baranello, Russell J. Butterfield, IA Horrocks, Helen Roper, Z. Alhaswani, Kevin M. Flanigan, Nancy L. Kuntz, Adnan Manzur, Basil T. Darras, Peter B. Kang, Leslie Morrison, Monika Krzesniak‐Swinarska, Jean K. Mah, Tiziana Mongini, Federica Ricci, Maja von der Hagen, Richard S. Finkel, Kathleen O’Reardon
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.