Large-scale serum protein biomarkers discovery associated with function and clinical milestones in Duchenne muscular dystrophy

N. A. Ikelaar, A. M. Barnard, S.W.M. Eng, Shahrzad Hosseini Vajargah, K.C.H. Ha, H. E. Kan, K. Vandenborne, E. H. Niks, G. A. Walter () and P. Spitali ()
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N. A. Ikelaar: Leiden University Medical Center
A. M. Barnard: University of Florida
S.W.M. Eng: BioSymetrics, Inc
Shahrzad Hosseini Vajargah: BioSymetrics, Inc
K.C.H. Ha: BioSymetrics, Inc
H. E. Kan: Duchenne Center Netherlands
K. Vandenborne: University of Florida
E. H. Niks: Leiden University Medical Center
G. A. Walter: University of Florida
P. Spitali: Leiden University Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting and weakness. Serum proteins may offer insight into disease processes and clinical decline. This observational study uses the 7 K SomaScan® assay to discover serum proteins associated with muscle function and disease milestones. In total 702 serum samples from 153 male patients, collected across two centers (2009–2022), are analyzed. Using linear mixed effects modelling, we evaluate age and corticosteroid use as covariates affecting protein levels and assess protein correlations with longitudinal clinical function. Here we show 318 aptamers (294 proteins) significantly associated with motor performance across the two sites, with most associations found with lower limb functional tests (NSAA, 10MRW, and 6MWT). Thirty-six proteins are associated with milestones including RGMA, ART3, ANTXR2, and DLK1. These proteins show promise as prognostic biomarkers, and could potentially be used for patient stratification in clinical trial design and for monitoring interventions.

Date: 2025
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DOI: 10.1038/s41467-025-64146-y

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