Conjugation of mannose 6-phosphate-containing oligosaccharides to acid alpha-glucosidase improves the clearance of glycogen in pompe mice

The Journal of Biological Chemistry
Yunxiang ZhuSeng H Cheng

Abstract

Clinical studies of enzyme replacement therapy for Pompe disease have indicated that relatively high doses of recombinant human acid alpha-glucosidase (rhGAA) may be required to reduce the abnormal glycogen storage in cardiac and skeletal muscles. This may be because of inefficient cation-independent mannose 6-phosphate receptor (CI-MPR)-mediated endocytosis of the enzyme by the affected target cells. To address this possibility, we examined whether the addition of a high affinity ligand to rhGAA would improve its delivery to these cells. Chemical conjugation of high mannose oligosaccharides harboring mono- and bisphosphorylated mannose 6-phosphates onto rhGAA (neo-rhGAA) significantly improved its uptake characteristics by muscle cells in vitro. Infusion of neo-rhGAA into Pompe mice also resulted in greater delivery of the enzyme to muscle tissues when compared with the unmodified enzyme. Importantly, this increase in enzyme levels was associated with significantly improved clearance of glycogen ( approximately 5-fold) from the affected tissues. These results suggest that CI-MPR-mediated endocytosis of rhGAA is an important pathway by which the enzyme is delivered to the affected lysosomes of Pompe muscle cells. Hence, the gen...Continue Reading

References

Aug 14, 1996·Biochimica Et Biophysica Acta·A G BijvoetM P Verbeet
Mar 21, 1998·The Journal of Clinical Investigation·T KikuchiY T Chen
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·A AmalfitanoY T Chen
Sep 14, 1999·European Journal of Human Genetics : EJHG·M G AusemsA T van der Ploeg
Aug 10, 2000·The Journal of Pediatrics·A E SlonimF Martiniuk
Sep 6, 2000·Lancet·H Van den HoutA T Van der Ploeg
Jan 5, 2002·Journal of Inherited Metabolic Disease·R O BradyR Schiffmann
Apr 13, 2002·Current Molecular Medicine·Nina RabenBarry J Byrne
Oct 10, 2002·European Journal of Pediatrics·Arnold J J ReuserAns T Van Der Ploeg
Sep 2, 2003·Developmental Medicine and Child Neurology·Stephen M HaleyAlison M Skrinar
Aug 1, 1960·Archives of Biochemistry and Biophysics·R F ANDERSONM E SLODKI
Oct 22, 2003·Molecular Genetics and Metabolism·N RabenP H Plotz
Feb 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jonathan H LeBowitzWilliam S Sly
Mar 30, 2004·Annals of Neurology·Léon P F WinkelAns T Van der Ploeg
May 4, 2004·Pediatrics·Johanna M P Van den HoutAns T Van der Ploeg

❮ Previous
Next ❯

Citations

Mar 23, 2011·Bioconjugate Chemistry·Qun ZhouClark Q Pan
Mar 12, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yunxiang ZhuSeng H Cheng
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ha T HuynhWilliam S Sly
Jan 18, 2006·Annual Review of Medicine·Roscoe O Brady
Feb 6, 2014·Chemical Reviews·María L VillalongaReynaldo Villalonga
Sep 14, 2012·Annual Review of Genomics and Human Genetics·R J Desnick, E H Schuchman
Jan 15, 2015·Annual Review of Medicine·Giancarlo ParentiAndrea Ballabio
Apr 9, 2016·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Mark TarnopolskyAneal Khan
May 14, 2016·ACS Chemical Biology·Phillip M Danby, Stephen G Withers
Jan 10, 2006·Molecular & Cellular Proteomics : MCP·David E SleatPeter Lobel
Oct 28, 2016·Chemical Communications : Chem Comm·Y SunM Nitz
Jan 16, 2010·Annals of the New York Academy of Sciences·Steven KozlowskiRaymond P Donnelly
Jan 19, 2012·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Emanuela LacanáAmy S Rosenberg
Mar 15, 2016·Angewandte Chemie·Pragya PriyankaAntony J Fairbanks
Jul 31, 2020·Nature·Steven M BanikCarolyn R Bertozzi
Jan 19, 2012·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Priya S KishnaniNancy J Mendelsohn
Dec 20, 2008·Chemical Reviews·David P GamblinBenjamin G Davis
May 3, 2021·Current Opinion in Chemical Biology·Nikki DellasGjalt W Huisman
May 27, 2021·Nature Chemical Biology·Thomas Whitmarsh-Everiss, Luca Laraia
Jul 24, 2021·ChemMedChem·Bhavana RamadasDebasish Manna
Aug 25, 2018·Chemical Reviews·Chao Li, Lai-Xi Wang
Aug 18, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Andrew D BaikKatherine D Cygnar
Oct 22, 2008·Lancet·Ans T van der Ploeg, Arnold J J Reuser
Oct 1, 2021·Drugs·Sohita Dhillon

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.