Document Type

Article

Publication Date

11-14-2025

Keywords

Duchenne muscular dystrophy, Proteomics, SomaScan, Biomarker discovery-validation, Serum-muscle omics integration

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.

Comments

https://doi.org/10.1038/s41598-025-23758-6

Publisher Attribution

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Download

Share

COinS