Researchers discovered a strong association between increased expression of the well-known atrogene BNIP3 and progressive muscle fiber atrophy in patients with late-onset Pompe disease (LOPD), as published in the American Journal of Pathology.

The study revealed a cascade starting with AKT-mTOR pathway inhibition, which resulted in increased expression of BNIP3 and smaller vacuolated fibers and myotubes in patients with LOPD.

“We report compelling evidence that supports the role of BNIP3 in the process of muscle fiber atrophy in LOPD patients,” the authors wrote. “Our data suggest that inhibition of the AKT-mTOR pathway activates BNIP3 expression, which perpetuates autophagy and probably induces muscle fiber atrophy.”


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The research team employed immunofluorescence and real-time polymerase chain reaction to study molecule expression related to muscle fiber atrophy in biopsies obtained from patients with LOPD. In addition to increased BNIP3 expression in the patients’ muscles, they observed ongoing atrophic processes in myotubes obtained from myoblasts of patients with LOPD.

The authors also transfected BNIP3 into healthy control myoblasts, which resulted in smaller myotubes than those differentiated from myotubes that were not transfected. Related studies have also found increased expression of BNIP3 in the muscles of patients with LOPD prior to starting treatment and to a lesser extent after enzyme replacement therapy initiation.

The authors note that the prostaglandin E1 analog misoprostol has recently been shown to modulate BNIP3 function in certain cell populations, and the current findings of this study suggest that regulation of BNIP3 activity through novel therapeutic approaches such as misoprostol or similar treatments could be an effective complementary strategy to reduce autophagy and muscle atrophy in LOPD.

Reference

Carrasco-Rozas A, Fernández-Simón E, Suárez-Calvet X, et al. BNIP3 is involved in muscle fiber atrophy in late-onset Pompe disease patients. Am J Pathol. Published online May 20, 2022. doi:10.1016/j.ajpath.2022.05.003