Identification of muscle biomarkers in McArdle disease

Glycogen storage disease type V (GSDV, McArdle disease) is a rare genetic myopathy caused by deficiency of the muscle isoform of glycogen phosphorylase (PYGM). This results in a block in the use of muscle glycogen as an energetic substrate, with subsequent exercise intolerance. The GSDV pathophysiology is still not fully understood, especially with regard to some features such as muscle contractures or persistent muscle damage (i.e., even without prior exercise). We aimed at identifying muscle protein biomarkers of GSDV by analyzing the muscle proteome and the molecular networks associated with muscle dysfunction. Muscle biopsies from 8 patients and 8 controls were studied by quantitative protein expression using isobaric tags for relative and absolute quantitation (iTRAQ) followed by artificial neuronal networks (ANNs) and topology analysis. Protein candidate validation was performed by western-blot. Several proteins predominantly involved in the process of muscle contraction and/or calcium homeostasis, such as myosin, sarcoplasmic/endoplasmic reticulum calcium ATPase 1, tropomyosin alpha-1 chain, tro-ponin isoforms, and alpha-actinin-3 showed significantly lower expression levels in muscle of GSDV patients. These proteins could be potential biomarkers of the persistent muscle damage reported in GSDV patients. Further studies are needed to elucidate the molecular mechanisms by which PYGM controls the expression of these proteins.