Gene expression profile of tibialis anterior from Gaa-/- mice compared to wild type mice

These membrane repair-associated proteins displayed abnormal localization during disease progression, with sarcoplasmic accumulation associated with T-tubules, lysosomes and autophagosomes, respectively. Analysis of muscle biopsies from some patients with late-onset Pompe disease (LOPD) identified similar expression patterns in moderately affected cases, whereas these patterns were less evident or absent in the most severe samples, suggesting stage-dependent redistribution associated with advanced myoarchitectural disorganization.

Furthermore, in the mouse model, we observed persistent post-transcriptional accumulation of mature myostatin (MSTN), a key negative regulator of muscle growth, alongside a decrease in the phospho-SMAD3/SMAD3 ratio and reduced SMAD7 expression, which point toward a more complex modulation of its canonical bioactivity rather than a simple increase. Altogether, these findings identify modified distribution proteins linked to membrane repair and dysregulation of MSTN as features of muscle remodeling in Pompe disease.