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

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Date
2011-06
Authors
Koeberl, Dwight D
Luo, Xiaoyan
Sun, Baodong
McVie-Wylie, Alison
Dai, Jian
Li, Songtao
Banugaria, Suhrad G
Chen, Y-T
Bali, Deeksha S
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(9 total)
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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.
Type
Journal article
Subject
Adrenergic beta-Agonists
Animals
Clenbuterol
Disease Models, Animal
Enzyme Replacement Therapy
Glycogen
Glycogen Storage Disease Type II
Male
Mice
Mice, Knockout
Motor Activity
Muscle, Skeletal
Receptor, IGF Type 2
alpha-Glucosidases
Permalink
https://hdl.handle.net/10161/15090
Published Version (Please cite this version)
10.1016/j.ymgme.2011.02.006
Publication Info
Koeberl, Dwight D; Luo, Xiaoyan; Sun, Baodong; McVie-Wylie, Alison; Dai, Jian; Li, Songtao; ... Bali, Deeksha S (2011). Enhanced efficacy of enzyme replacement therapy in Pompe disease through mannose-6-phosphate receptor expression in skeletal muscle. Mol Genet Metab, 103(2). pp. 107-112. 10.1016/j.ymgme.2011.02.006. Retrieved from https://hdl.handle.net/10161/15090.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Bali

Deeksha Sarihyan Bali

Professor of Pediatrics
1)Development of new non-invasive laboratory diagnostic methods using enzymology and molecular diagnostic techniques for Glycogen Storage Diseases (GSDs) and Lysosomal Storage Diseases (LSDs) like Pompe, Fabry, Gaucher, MPS - for early diagnosis and treatment modalities. Exploration of new high throughput diagnostic platforms with an idea of implementation into New born screening (NBS)of these diseases. 2)Clinical research studies associated with Pompe disease with a goal to improve

Yuan-Tsong Chen

Professor Emeritus of Pediatrics
Our overall research interests are in translational research. We aim at translating the promise of genomic medicine into clinical reality. Specific projects at present time include: 1). Identification of novel genes/targets associated with human diseases. This includes susceptibility genes for common multi-factorial diseases and adverse drug reactions. Genetic epidemiology, mouse ENU mutagenesis, bioinformatics and proteomics are some approaches that we use in identific
Koeberl

Dwight D. Koeberl

Professor of Pediatrics
As a physician-scientist practicing clinical and biochemical genetics, I am highly motivated to seek improved therapy for my patients with inherited disorders of metabolism. The focus of our research has been the development of gene therapy with adeno-associated virus (AAV) vectors, most recently by genome editing with CRISPR/Cas9. We have developed gene therapy for inherited disorders of metabolism, especially glycogen storage disease (GSD) and phenylketonuria (PKU).  1) GSD
Sun

Baodong Sun

Associate Professor in Pediatrics
My overall research interests are finding effective treatment for human glycogen storage diseases (GSDs) and other inherited metabolic disorders. My current research focuses on identification of novel therapeutic targets and development of effective therapies for GSD II (Pompe disease), GSD III (Cori disease), and GSD IV (Andersen disease) using cellular and animal disease models. The main therapeutic approaches we are using in our pre-clinical studie
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