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Differential muscular glycogen clearance after enzyme replacement therapy in a mouse model of Pompe disease.
Mol Genet Metab 2007; 91(4):343-51MG

Abstract

Glycogen storage disease in the alpha-glucosidase knockout(6neo(-)/6neo(-)) (GAA KO) mouse, a model of Pompe disease, results in the pathologic accumulation of glycogen primarily within skeletal myocytes and cardiomyocytes. Intravenous administration of recombinant human alpha-glucosidase (rhGAA, Myozyme, aglucosidase alfa) can result in significant glycogen clearance from both cardiomyocytes and skeletal myocytes, however, the degree of clearance varies from one skeletal muscle type to another. We sought to determine what role muscle fiber type predominance played in this variability. To examine this question in the GAA KO mouse model we delivered intravenous doses of 100 mg/kg rhGAA on Day 1, and Day 14, and harvested a variety of fast and slow twitch muscles on Day 28. We measured glycogen clearance, muscle fiber type content and capillary density by light microscopy with computer morphometry. Recombinant human-GAA administration resulted in differential clearance of glycogen in the various muscles examined. Slow twitch-predominant muscles cleared glycogen significantly more efficiently than fast twitch-predominant muscles. There was a strong correlation between capillary density and glycogen clearance (r=0.55), suggesting that at the high doses used in this study the differential glycogen clearance observed between muscles is largely due to differential bioavailability of rhGAA regulated by blood flow.

Authors+Show Affiliations

Department of Pathology, Genzyme Corporation, 1 Mountain Rd., P.O. Box 9322, Framingham, MA 01701-9322, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17572127

Citation

Hawes, Michael L., et al. "Differential Muscular Glycogen Clearance After Enzyme Replacement Therapy in a Mouse Model of Pompe Disease." Molecular Genetics and Metabolism, vol. 91, no. 4, 2007, pp. 343-51.
Hawes ML, Kennedy W, O'Callaghan MW, et al. Differential muscular glycogen clearance after enzyme replacement therapy in a mouse model of Pompe disease. Mol Genet Metab. 2007;91(4):343-51.
Hawes, M. L., Kennedy, W., O'Callaghan, M. W., & Thurberg, B. L. (2007). Differential muscular glycogen clearance after enzyme replacement therapy in a mouse model of Pompe disease. Molecular Genetics and Metabolism, 91(4), pp. 343-51.
Hawes ML, et al. Differential Muscular Glycogen Clearance After Enzyme Replacement Therapy in a Mouse Model of Pompe Disease. Mol Genet Metab. 2007;91(4):343-51. PubMed PMID: 17572127.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential muscular glycogen clearance after enzyme replacement therapy in a mouse model of Pompe disease. AU - Hawes,Michael L, AU - Kennedy,William, AU - O'Callaghan,Michael W, AU - Thurberg,Beth L, Y1 - 2007/06/14/ PY - 2007/04/26/received PY - 2007/04/27/accepted PY - 2007/6/19/pubmed PY - 2007/10/25/medline PY - 2007/6/19/entrez SP - 343 EP - 51 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 91 IS - 4 N2 - Glycogen storage disease in the alpha-glucosidase knockout(6neo(-)/6neo(-)) (GAA KO) mouse, a model of Pompe disease, results in the pathologic accumulation of glycogen primarily within skeletal myocytes and cardiomyocytes. Intravenous administration of recombinant human alpha-glucosidase (rhGAA, Myozyme, aglucosidase alfa) can result in significant glycogen clearance from both cardiomyocytes and skeletal myocytes, however, the degree of clearance varies from one skeletal muscle type to another. We sought to determine what role muscle fiber type predominance played in this variability. To examine this question in the GAA KO mouse model we delivered intravenous doses of 100 mg/kg rhGAA on Day 1, and Day 14, and harvested a variety of fast and slow twitch muscles on Day 28. We measured glycogen clearance, muscle fiber type content and capillary density by light microscopy with computer morphometry. Recombinant human-GAA administration resulted in differential clearance of glycogen in the various muscles examined. Slow twitch-predominant muscles cleared glycogen significantly more efficiently than fast twitch-predominant muscles. There was a strong correlation between capillary density and glycogen clearance (r=0.55), suggesting that at the high doses used in this study the differential glycogen clearance observed between muscles is largely due to differential bioavailability of rhGAA regulated by blood flow. SN - 1096-7192 UR - https://www.unboundmedicine.com/medline/citation/17572127/Differential_muscular_glycogen_clearance_after_enzyme_replacement_therapy_in_a_mouse_model_of_Pompe_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(07)00143-6 DB - PRIME DP - Unbound Medicine ER -