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Enhanced efficacy of enzyme replacement therapy in Pompe disease through mannose-6-phosphate receptor expression in skeletal muscle.

dc.contributor.author Bali, Deeksha Sarihyan
dc.contributor.author Banugaria, SG
dc.contributor.author Chen, Y-T
dc.contributor.author Dai, J
dc.contributor.author Koeberl, Dwight D
dc.contributor.author Li, S
dc.contributor.author Luo, X
dc.contributor.author McVie-Wylie, A
dc.contributor.author Sun, Baodong
dc.coverage.spatial United States
dc.date.accessioned 2017-07-24T14:43:19Z
dc.date.available 2017-07-24T14:43:19Z
dc.date.issued 2011-06
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/21397538
dc.identifier S1096-7192(11)00049-7
dc.identifier.uri http://hdl.handle.net/10161/15090
dc.description.abstract Enzyme replacement therapy (ERT) with acid α-glucosidase has become available for Pompe disease; however, the response of skeletal muscle, as opposed to the heart, has been attenuated. The poor response of skeletal muscle has been attributed to the low abundance of the cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle compared to heart. To further understand the role of CI-MPR in Pompe disease, muscle-specific CI-MPR conditional knockout (KO) mice were crossed with GAA-KO (Pompe disease) mice. We evaluated the impact of CI-MPR-mediated uptake of GAA by evaluating ERT in CI-MPR-KO/GAA-KO (double KO) mice. The essential role of CI-MPR was emphasized by the lack of efficacy of ERT as demonstrated by markedly reduced biochemical correction of GAA deficiency and of glycogen accumulations in double KO mice, in comparison with the administration of the same therapeutic doses in GAA-KO mice. Clenbuterol, a selective β(2)-agonist, enhanced the CI-MPR expression in skeletal tissue and also increased efficacy from GAA therapy, thereby confirming the key role of CI-MPR with regard to enzyme replacement therapy in Pompe disease. Biochemical correction improved in both muscle and non-muscle tissues, indicating that therapy could be similarly enhanced in other lysosomal storage disorders. In summary, enhanced CI-MPR expression might improve the efficacy of enzyme replacement therapy in Pompe disease through enhancing receptor-mediated uptake of GAA.
dc.language eng
dc.relation.ispartof Mol Genet Metab
dc.relation.isversionof 10.1016/j.ymgme.2011.02.006
dc.subject Adrenergic beta-Agonists
dc.subject Animals
dc.subject Clenbuterol
dc.subject Disease Models, Animal
dc.subject Enzyme Replacement Therapy
dc.subject Glycogen
dc.subject Glycogen Storage Disease Type II
dc.subject Male
dc.subject Mice
dc.subject Mice, Knockout
dc.subject Motor Activity
dc.subject Muscle, Skeletal
dc.subject Receptor, IGF Type 2
dc.subject alpha-Glucosidases
dc.title Enhanced efficacy of enzyme replacement therapy in Pompe disease through mannose-6-phosphate receptor expression in skeletal muscle.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/21397538
pubs.begin-page 107
pubs.end-page 112
pubs.issue 2
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Pediatrics
pubs.organisational-group Pediatrics, Medical Genetics
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 103
dc.identifier.eissn 1096-7206


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