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

ABSTRACT: 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

SUBMITTER: Han SO 

PROVIDER: S-EPMC7002209 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature