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

dc.contributor.author

Koeberl, Dwight D

dc.contributor.author

Luo, Xiaoyan

dc.contributor.author

Sun, Baodong

dc.contributor.author

McVie-Wylie, Alison

dc.contributor.author

Dai, Jian

dc.contributor.author

Li, Songtao

dc.contributor.author

Banugaria, Suhrad G

dc.contributor.author

Chen, Y-T

dc.contributor.author

Bali, Deeksha S

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.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.identifier

https://www.ncbi.nlm.nih.gov/pubmed/21397538

dc.identifier

S1096-7192(11)00049-7

dc.identifier.eissn

1096-7206

dc.identifier.uri

https://hdl.handle.net/10161/15090

dc.language

eng

dc.publisher

Elsevier BV

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

duke.contributor.orcid

Koeberl, Dwight D|0000-0003-4513-2464

duke.contributor.orcid

Sun, Baodong|0000-0002-2191-0025

duke.contributor.orcid

Bali, Deeksha S|0000-0003-2550-8073

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

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
2011-Enhanced efficacy of enzyme replacement therapy in Pompe disease through mannose-6-phosphate receptor.pdf
Size:
1.83 MB
Format:
Adobe Portable Document Format