A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease.

ABSTRACT: Enzyme replacement therapy (ERT) with recombinant human acid ?-glucosidase (rhGAA) fails to completely reverse muscle weakness in Pompe disease. ?2-agonists enhanced ERT by increasing receptor-mediated uptake of rhGAA in skeletal muscles.To test the hypothesis that a ?-blocker might reduce the efficacy of ERT, because the action of ?-blockers opposes those of ?2-agonists.Mice with Pompe disease were treated with propranolol (a ?-blocker) or clenbuterol in combination with ERT, or with ERT alone.Propranolol-treated mice had decreased weight gain (p<0.01), in comparison with clenbuterol-treated mice. Left ventricular mass was decreased (and comparable to wild-type) in ERT only and clenbuterol-treated groups of mice, and unchanged in propranolol-treated mice. GAA activity increased following either clenbuterol or propranolol in skeletal muscles. However, muscle glycogen was reduced only in clenbuterol-treated mice, not in propranolol-treated mice. Cell-based experiments confirmed that propranolol reduces uptake of rhGAA into Pompe fibroblasts and also demonstrated that the drug induces intracellular accumulation of glycoproteins at higher doses.Propranolol, a commonly prescribed ?-blocker, reduced weight, increased left ventricular mass and decreased glycogen clearance in skeletal muscle following ERT. ?-Blockers might therefore decrease the efficacy from ERT in patients with Pompe disease.

SUBMITTER: Han SO 

PROVIDER: S-EPMC4755835 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature