Evaluation of antihypertensive drugs in combination with enzyme replacement therapy in mice with Pompe disease.

Journal Article (Journal Article)

Pompe disease is caused by the deficiency of lysosomal acid α-glucosidase (GAA) leading to progressive myopathy. Enzyme replacement therapy (ERT) with recombinant human (rh) GAA has limitations, including inefficient uptake of rhGAA in skeletal muscle linked to low cation-independent mannose-6-phosphate receptor (CI-MPR) expression. PURPOSE: To test the hypothesis that antihypertensive agents causing muscle hypertrophy by increasing insulin-like growth factor 1 expression can increase CI-MPR-mediated uptake of recombinant enzyme with therapeutic effects in skeletal muscle. METHODS: Three such agents were evaluated in mice with Pompe disease (carvedilol, losartan, and propranolol), either with or without concurrent ERT. RESULTS: Carvedilol, a selective β-blocker, increased muscle strength but reduced biochemical correction from ERT. Administration of drugs alone had minimal effect, with the exception of losartan that increased glycogen storage and mortality either by itself or in combination with ERT. CONCLUSION: The β-blocker carvedilol had beneficial effects during ERT in mice with Pompe disease, in comparison with propranolol or losartan. Caution is warranted when prescribing antihypertensive drugs in Pompe disease.

Full Text

Duke Authors

Cited Authors

  • Han, S-O; Haynes, AC; Li, S; Abraham, DM; Kishnani, PS; Steet, R; Koeberl, DD

Published Date

  • February 2020

Published In

Volume / Issue

  • 129 / 2

Start / End Page

  • 73 - 79

PubMed ID

  • 31645300

Pubmed Central ID

  • PMC7002209

Electronic International Standard Serial Number (EISSN)

  • 1096-7206

Digital Object Identifier (DOI)

  • 10.1016/j.ymgme.2019.10.005


  • eng

Conference Location

  • United States