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A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease.
Mol Genet Metab 2016; 117(2):114-9MG

Abstract

Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) fails to completely reverse muscle weakness in Pompe disease. β2-agonists enhanced ERT by increasing receptor-mediated uptake of rhGAA in skeletal muscles.

PURPOSE

To test the hypothesis that a β-blocker might reduce the efficacy of ERT, because the action of β-blockers opposes those of β2-agonists.

METHODS

Mice with Pompe disease were treated with propranolol (a β-blocker) or clenbuterol in combination with ERT, or with ERT alone.

RESULTS

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.

CONCLUSION

Propranolol, a commonly prescribed β-blocker, reduced weight, increased left ventricular mass and decreased glycogen clearance in skeletal muscle following ERT. β-Blockers might therefore decrease the efficacy from ERT in patients with Pompe disease.

Authors+Show Affiliations

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States.Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States.Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States.Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States.Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States.Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26454691

Citation

Han, Sang-Oh, et al. "A Beta-blocker, Propranolol, Decreases the Efficacy From Enzyme Replacement Therapy in Pompe Disease." Molecular Genetics and Metabolism, vol. 117, no. 2, 2016, pp. 114-9.
Han SO, Pope R, Li S, et al. A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease. Mol Genet Metab. 2016;117(2):114-9.
Han, S. O., Pope, R., Li, S., Kishnani, P. S., Steet, R., & Koeberl, D. D. (2016). A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease. Molecular Genetics and Metabolism, 117(2), pp. 114-9. doi:10.1016/j.ymgme.2015.09.012.
Han SO, et al. A Beta-blocker, Propranolol, Decreases the Efficacy From Enzyme Replacement Therapy in Pompe Disease. Mol Genet Metab. 2016;117(2):114-9. PubMed PMID: 26454691.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease. AU - Han,Sang-Oh, AU - Pope,Rand, AU - Li,Songtao, AU - Kishnani,Priya S, AU - Steet,Richard, AU - Koeberl,Dwight D, Y1 - 2015/10/03/ PY - 2015/09/29/received PY - 2015/09/30/accepted PY - 2015/10/12/entrez PY - 2015/10/12/pubmed PY - 2016/11/4/medline KW - Acid α-glucosidase (GAA) KW - Enzyme replacement therapy (ERT) KW - Lysosomal storage disorder (LSD) KW - Pompe disease KW - Propranolol KW - β-Blocker SP - 114 EP - 9 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 117 IS - 2 N2 - UNLABELLED: Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) fails to completely reverse muscle weakness in Pompe disease. β2-agonists enhanced ERT by increasing receptor-mediated uptake of rhGAA in skeletal muscles. PURPOSE: To test the hypothesis that a β-blocker might reduce the efficacy of ERT, because the action of β-blockers opposes those of β2-agonists. METHODS: Mice with Pompe disease were treated with propranolol (a β-blocker) or clenbuterol in combination with ERT, or with ERT alone. RESULTS: 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. CONCLUSION: Propranolol, a commonly prescribed β-blocker, reduced weight, increased left ventricular mass and decreased glycogen clearance in skeletal muscle following ERT. β-Blockers might therefore decrease the efficacy from ERT in patients with Pompe disease. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/26454691/A_beta_blocker_propranolol_decreases_the_efficacy_from_enzyme_replacement_therapy_in_Pompe_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(15)30058-5 DB - PRIME DP - Unbound Medicine ER -