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Serum and urine proteomic profiling reveals biomarkers suitable for monitoring the outcome of therapeutic interventions in muscular dystrophies
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Edité par CCSD -
International audience. Therapy-responsive biomarkers are an important need in the muscular dystrophy field where new treatments are currently in clinical trials. In the present study, serum samples from Duchenne muscular dystrophy (DMD) patients and their respective age-matched controls (77 individuals) collected in the frame of the ADNA program (Advanced Diagnostic for New therapeutic Approaches) were analyzed by a comprehensive high-resolution mass spectrometry approach. Several proteins and protein fragments were found to be abnormally present in sera and urines of DMD patients, limb-girdle muscular dystrophy type 2D (LGMD2D) and their respective animal models. Levels of one the found biomarker, fragments of the myofibrillar structural protein myomesin-3 (MYOM3) were assayed in therapeutic model systems where stable restoration of α-sarcoglycan expression in KO-SGCA mice was achieved by systemic injection of a viral vector. Following administration of the therapeutic agents MYOM3 was restored toward wild-type levels in a dose-dependent manner. MYOM3 fragments showed lower inter-individual variability compared with the commonly used creatine kinase assay, and correlated better with the restoration of the dystrophin-associated protein complex and muscle force. These data suggest that the MYOM3 fragments hold promise for minimally invasive assessment of experimental therapies for DMD and other neuromuscular disorders.
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