Universal Proteomic Signature After Exercise‐Induced Muscle Injury in Muscular Dystrophies

ABSTRACT Objective Several neuromuscular disorders (NMDs) are characterized by progressive muscle damage and are marked by the elevation of circulating muscle proteins from activity‐related injury. Despite a diverse array of genetic drivers, many NMDs share similar patterns of exercise intolerance a...

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Main Authors: Mads G. Stemmerik, Benjamin Barthel, Nanna R. Andersen, Sofie V. Skriver, Alan J. Russell, John Vissing
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Annals of Clinical and Translational Neurology
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Online Access:https://doi.org/10.1002/acn3.70035
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Summary:ABSTRACT Objective Several neuromuscular disorders (NMDs) are characterized by progressive muscle damage and are marked by the elevation of circulating muscle proteins from activity‐related injury. Despite a diverse array of genetic drivers, many NMDs share similar patterns of exercise intolerance and higher concentrations of muscle injury proteins relative to unaffected individuals. While the interplay between the nature of the muscle injury and the specific genetic driver is poorly understood, the similarities exhibited by various NMDs suggest that a common proteomic signature of muscle injury may exist. Methods We used an established exercise challenge and the SOMAscan proteomics platform to study the baseline and post‐exercise proteomic profiles in a cross‐sectional study of three different muscular dystrophies: Becker muscular dystrophy (BMD) and limb girdle muscular dystrophy types R9 and R12. Results Our Results Uncover a Common Signature of Circulating Proteins That Are Elevated in all Three Myopathies, Some of Which Are Further Elevated by Exercise in Becker Muscular Dystrophy and Limb Girdle Muscular Dystrophy Type R9, and Others That Are Not Responsive to Exercise. Interpretation Interestingly, these two signatures exhibit opposing trajectories with age in a larger cross‐sectional cohort of BMD individuals. This research represents a first step toward defining an annotated protein signature coupled with activity‐injury, a defining pathophysiological feature of many myopathies.
ISSN:2328-9503