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Glycosylation-independent lysosomal targeting of acid α-glucosidase enhances muscle glycogen clearance in pompe mice.
J Biol Chem. 2013 Jan 18; 288(3):1428-38.JB

Abstract

We have used a peptide-based targeting system to improve lysosomal delivery of acid α-glucosidase (GAA), the enzyme deficient in patients with Pompe disease. Human GAA was fused to the glycosylation-independent lysosomal targeting (GILT) tag, which contains a portion of insulin-like growth factor II, to create an active, chimeric enzyme with high affinity for the cation-independent mannose 6-phosphate receptor. GILT-tagged GAA was taken up by L6 myoblasts about 25-fold more efficiently than was recombinant human GAA (rhGAA). Once delivered to the lysosome, the mature form of GILT-tagged GAA was indistinguishable from rhGAA and persisted with a half-life indistinguishable from rhGAA. GILT-tagged GAA was significantly more effective than rhGAA in clearing glycogen from numerous skeletal muscle tissues in the Pompe mouse model. The GILT-tagged GAA enzyme may provide an improved enzyme replacement therapy for Pompe disease patients.

Authors+Show Affiliations

ZyStor Therapeutics, Milwaukee, Wisconsin 53226-4838, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23188827

Citation

Maga, John A., et al. "Glycosylation-independent Lysosomal Targeting of Acid Α-glucosidase Enhances Muscle Glycogen Clearance in Pompe Mice." The Journal of Biological Chemistry, vol. 288, no. 3, 2013, pp. 1428-38.
Maga JA, Zhou J, Kambampati R, et al. Glycosylation-independent lysosomal targeting of acid α-glucosidase enhances muscle glycogen clearance in pompe mice. J Biol Chem. 2013;288(3):1428-38.
Maga, J. A., Zhou, J., Kambampati, R., Peng, S., Wang, X., Bohnsack, R. N., Thomm, A., Golata, S., Tom, P., Dahms, N. M., Byrne, B. J., & LeBowitz, J. H. (2013). Glycosylation-independent lysosomal targeting of acid α-glucosidase enhances muscle glycogen clearance in pompe mice. The Journal of Biological Chemistry, 288(3), 1428-38. https://doi.org/10.1074/jbc.M112.438663
Maga JA, et al. Glycosylation-independent Lysosomal Targeting of Acid Α-glucosidase Enhances Muscle Glycogen Clearance in Pompe Mice. J Biol Chem. 2013 Jan 18;288(3):1428-38. PubMed PMID: 23188827.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glycosylation-independent lysosomal targeting of acid α-glucosidase enhances muscle glycogen clearance in pompe mice. AU - Maga,John A, AU - Zhou,Jianghong, AU - Kambampati,Ravi, AU - Peng,Susan, AU - Wang,Xu, AU - Bohnsack,Richard N, AU - Thomm,Angela, AU - Golata,Sarah, AU - Tom,Peggy, AU - Dahms,Nancy M, AU - Byrne,Barry J, AU - LeBowitz,Jonathan H, Y1 - 2012/11/27/ PY - 2012/11/29/entrez PY - 2012/11/29/pubmed PY - 2013/3/27/medline SP - 1428 EP - 38 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 288 IS - 3 N2 - We have used a peptide-based targeting system to improve lysosomal delivery of acid α-glucosidase (GAA), the enzyme deficient in patients with Pompe disease. Human GAA was fused to the glycosylation-independent lysosomal targeting (GILT) tag, which contains a portion of insulin-like growth factor II, to create an active, chimeric enzyme with high affinity for the cation-independent mannose 6-phosphate receptor. GILT-tagged GAA was taken up by L6 myoblasts about 25-fold more efficiently than was recombinant human GAA (rhGAA). Once delivered to the lysosome, the mature form of GILT-tagged GAA was indistinguishable from rhGAA and persisted with a half-life indistinguishable from rhGAA. GILT-tagged GAA was significantly more effective than rhGAA in clearing glycogen from numerous skeletal muscle tissues in the Pompe mouse model. The GILT-tagged GAA enzyme may provide an improved enzyme replacement therapy for Pompe disease patients. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/23188827/Glycosylation_independent_lysosomal_targeting_of_acid_α_glucosidase_enhances_muscle_glycogen_clearance_in_pompe_mice_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=23188827 DB - PRIME DP - Unbound Medicine ER -