Identification of novel protein biomarkers correlating with both cardiac and skeletal muscle indices in duchenne muscular dystrophy.

BackgroundDuchenne muscular dystrophy (DMD) is marked by cardiac and skeletal myopathy with disparate onset and progression suggesting distinct pathophysiologies. Nontargeted proteomics may elucidate the different disease pathways underlying skeletal muscle and cardiomyopathy progression and identify proteins that improve DMD risk stratification.Methods and resultsSixty subjects were enrolled; 56 underwent cardiac magnetic resonance to determine left ventricular ejection fraction, late gadolinium enhancement, and myocardial circumferential strain. Of the 60 patients enrolled, 51 underwent quantitative muscle testing and 33 underwent actigraphy. Aptamer-based technology (SomaScan) evaluated 1128 proteins in plasma. The correlations between serum protein levels and cardiac or skeletal muscle indices were tested using a Spearman correlation test followed by multiple testing correction yielding q-values. The median age was 15.0 years (12.7-17.9 interquartile range). Of 1128 proteins analyzed, 208 correlated with only cardiac indices; 14 correlated with only skeletal muscle indices; 10 proteins correlated strongly with both indices. Protein functions included (1) calcium regulation, (2) cardiac remodeling, (3) cell homeostasis, (4) fibrosis, (5) inflammation, (6) lipid regulation, and (7) other.ConclusionOur nontargeted proteomics study identified serum biomarkers correlating with skeletal and cardiac progression in DMD. Candidate proteins-some uniquely associated with skeletal or cardiac indices and others overlapping-offer promising leads for studies to improve risk stratification and guide targeted therapies in DMD.