Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy
dc.contributor.author | Marshall, John | |
dc.contributor.author | McEachern, Kerry Anne | |
dc.contributor.author | Chuang, Wei‐lien | |
dc.contributor.author | Hutto, Elizabeth | |
dc.contributor.author | Siegel, Craig S. | |
dc.contributor.author | Shayman, James A. | |
dc.contributor.author | Grabowski, Greg A. | |
dc.contributor.author | Scheule, Ronald K. | |
dc.contributor.author | Copeland, Diane P. | |
dc.contributor.author | Cheng, Seng H. | |
dc.date.accessioned | 2019-01-15T20:29:01Z | |
dc.date.available | 2019-01-15T20:29:01Z | |
dc.date.issued | 2010-06 | |
dc.identifier.citation | Marshall, John; McEachern, Kerry Anne; Chuang, Wei‐lien ; Hutto, Elizabeth; Siegel, Craig S.; Shayman, James A.; Grabowski, Greg A.; Scheule, Ronald K.; Copeland, Diane P.; Cheng, Seng H. (2010). "Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy." Journal of Inherited Metabolic Disease 33(3): 281-289. | |
dc.identifier.issn | 0141-8955 | |
dc.identifier.issn | 1573-2665 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/147062 | |
dc.description.abstract | Gaucher disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (acid βâ glucosidase), with consequent cellular accumulation of glucosylceramide (GLâ 1). The disease is managed by intravenous administrations of recombinant glucocerebrosidase (imiglucerase), although symptomatic patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy (ERT) is not an option may also be treated by substrate reduction therapy (SRT) with miglustat. To determine whether the sequential use of both ERT and SRT may provide additional benefits, we compared the relative pharmacodynamic efficacies of separate and sequential therapies in a murine model of Gaucher disease (D409V/null). As expected, ERT with recombinant glucocerebrosidase was effective in reducing the burden of GLâ 1 storage in the liver, spleen, and lung of 3â monthâ old Gaucher mice. SRT using a novel inhibitor of glucosylceramide synthase (Genzâ 112638) was also effective, albeit to a lesser degree than ERT. Animals administered recombinant glucocerebrosidase and then Genzâ 112638 showed the lowest levels of GLâ 1 in all the visceral organs and a reduced number of Gaucher cells in the liver. This was likely because the additional deployment of SRT following enzyme therapy slowed the rate of reaccumulation of GLâ 1 in the affected organs. Hence, in patients whose disease has been stabilized by intravenously administered recombinant glucocerebrosidase, orally administered SRT with Genzâ 112638 could potentially be used as a convenient maintenance therapy. In patients naïve to treatment, ERT followed by SRT could potentially accelerate clearance of the offending substrate. | |
dc.publisher | Wiley Periodicals, Inc. | |
dc.publisher | Springer Netherlands | |
dc.title | Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy | |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | |
dc.subject.hlbsecondlevel | Medicine (General) | |
dc.subject.hlbtoplevel | Health Sciences | |
dc.description.peerreviewed | Peer Reviewed | |
dc.description.bitstreamurl | https://deepblue.lib.umich.edu/bitstream/2027.42/147062/1/jimd0281.pdf | |
dc.identifier.doi | 10.1007/s10545-010-9072-z | |
dc.identifier.source | Journal of Inherited Metabolic Disease | |
dc.identifier.citedreference | Pastores GM, Giraldo P, Cherin P, Mehta A ( 2009 ) Goalâ oriented therapy with miglustat in Gaucher disease. Curr. Med. Res. Opin., 25: 23 â 37, 10.1185/03007990802576518 -->. | |
dc.identifier.citedreference | Jeyakumar M, Norflus F, Tifft CJ, et al ( 2001 ) Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation. Blood, 97: 327 â 329, 10.1182/blood.V97.1.327 -->. | |
dc.identifier.citedreference | Jeyakumar M, Dwek R, Butters T, Platt F ( 2005 ) Storage solutions: treating lysosomal disorders of the brain. Nat. Rev. Neurosci., 6: 713 â 725. | |
dc.identifier.citedreference | Kishnani PS DiRocco M Kaplan P et al A randomized trial comparing the efficacy and safety of imiglucerase (Cerezyme) infusions every 4 weeks versus every 2 weeks in the maintenance therapy of adult patients with Gaucher disease type 1 Mol. Genet. Med. 2009. | |
dc.identifier.citedreference | Langeveld M, Ghauharali KJM, Sauerwein HP, et al ( 2008 ) Type 1 Gaucher disease, a glycosphingolipid storage disorder, is associated with insulin resistance. J. Clin. Endocrinol. Metab., 93: 845 â 851, 10.1210/jc.2007‐1702 -->. | |
dc.identifier.citedreference | Lee L, Abe A, Shayman JA ( 1999 ) Improved inhibitors of glucosylceramide synthase. J. Biol. Chem., 274: 14662 â 14665, 10.1074/jbc.274.21.14662 -->. | |
dc.identifier.citedreference | Lieberman RL, Wustman BA, Huertas P, et al ( 2007 ) Structure of acidâ βâ glucosidase with pharmacological chaperone provides insight into Gaucher disease. Nature Chem Biol., 3: 101 â 107, 10.1038/nchembio850 -->. | |
dc.identifier.citedreference | McEachern K, Nietupski JB, Chuang Wâ L, et al ( 2006 ) AAV8â mediated expression of glucocerebrosidase ameliorates the storage pathology in the visceral organs of a mouse model of Gaucher disease. J. Gene. Med., 8: 719 â 729, 10.1002/jgm.901 -->. | |
dc.identifier.citedreference | McEachern KA, Fung J, Komarnitsky S, et al ( 2007 ) A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol. Genet. Metab., 91: 259 â 267, 10.1016/j.ymgme.2007.04.001 -->. | |
dc.identifier.citedreference | Mehta A ( 2008 ) Gaucher disease: unmet treatment needs. Acta Paediatr., 97: 83 â 87, 10.1111/j.1651‐2227.2008.00653.x -->. | |
dc.identifier.citedreference | Mu Tâ W, Ong DST, Wang Yâ J, Balch WE, Yates JR, Segatori L, Kelly JW ( 2008 ) Chemical and biological approaches synergize to ameliorate proteinâ folding diseases. Cell, 134: 769 â 761, 10.1016/j.cell.2008.06.037 -->. | |
dc.identifier.citedreference | Pastores GM, Barnett NL, Kolodny EH ( 2005 ) An openâ label, noncomparative study of miglustat in type 1 Gaucher disease: efficacy and tolerability over 24 months of treatment. Clin Ther., 27: 1215 â 1227, 10.1016/j.clinthera.2005.08.004 -->. | |
dc.identifier.citedreference | Platt FM, Neises GR, Reinkensmeier G, et al ( 1997 ) Prevention of lysosomal storage in Tayâ Sachs mice treated with Nâ butyldeoxynojirimycin. Science, 276: 428 â 431, 10.1126/science.276.5311.428 -->. | |
dc.identifier.citedreference | Shaaltiel Y, Bartfeld D, Hashmueli S, et al ( 2007 ) Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher’s disease using a plant cell system. Plant Biotechnol J., 5: 579 â 590, 10.1111/j.1467‐7652.2007.00263.x -->. | |
dc.identifier.citedreference | Starzyk K, Richards S, Yee J, Smith SE, Kingma W ( 2007 ) The longâ term international safety experience of imiglucerase therapy for Gaucher disease. Mol. Genet. Metab., 90: 157 â 163, 10.1016/j.ymgme.2006.09.003 -->. | |
dc.identifier.citedreference | Steet RA, Chung S, Wustman B, Powe A, Do H, Kornfeld SA ( 2006 ) The iminosugar isofagomine increases the activity of N370S mutant acid βâ glucosidase in Gaucher fibroblasts by several mechanisms. Proc. Natl. Acad. Sci. USA, 103: 13813 â 13818, 10.1073/pnas.0605928103 -->. | |
dc.identifier.citedreference | van Patten SM, Hughes H, Huff MR, et al ( 2007 ) Effect of mannose chain length on targeting of glucocerebrosidase for enzyme replacement therapy of Gaucher disease. Glycobiology, 17: 467 â 478, 10.1093/glycob/cwm008 -->. | |
dc.identifier.citedreference | Weinreb NJ, Charrow J, Andersson HC, et al ( 2002 ) Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2â 5 years of treatment: a report from the Gaucher Registry. Am. J. Med., 113: 112 â 119, 10.1016/S0002‐9343(02)01150‐6 -->. | |
dc.identifier.citedreference | Weinreb N, Taylor J, Cox T, Yee J, vom Dahl S ( 2008 ) A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase. Am. J. Hematol., 83: 890 â 895, 10.1002/ajh.21280 -->. | |
dc.identifier.citedreference | Wraith JE ( 2006 ) Limitations of enzyme replacement therapy; current and future. J. Inherit. Metab. Dis., 29: 442 â 447, 10.1007/s10545‐006‐0239‐6 -->. | |
dc.identifier.citedreference | Xu Yâ H, Quinn B, Witte D, Grabowski GA ( 2003 ) Viable mouse models of acid βâ glucosidase deficiency. Am. J. Pathol., 163: 2093 â 2101. | |
dc.identifier.citedreference | Yu Z, Sawkar AR, Whalen LJ, Wong Câ H, Kelly JW ( 2007 ) Isofagomineâ and 2, 5â anhydroâ 2, 5â iminoâ Dâ glucitolâ based glucocerebrosidase pharmacological chaperones for Gaucher disease intervention. J. Med. Chem., 50: 94 â 100, 10.1021/jm060677i -->. | |
dc.identifier.citedreference | Zhao H, Przybylska M, Wu Iâ H, et al ( 2007 ) Inhibiting glycosphingolipid synthesis improves glycemic control and insulin sensitivity in animal models of type 2 diabetes. Diabetes, 56: 1210 â 1218, 10.2337/db06‐0719 -->. | |
dc.identifier.citedreference | Zimran A Ilan Y Elstein D Enzyme replacement therapy for mild patients with Gaucher disease Am. J. Hematol. 2009. | |
dc.identifier.citedreference | Aerts JM, Ottenhoff R, Powlson AS, et al ( 2007 ) Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity. Diabetes, 56: 1341 â 1349, 10.2337/db06‐1619 -->. | |
dc.identifier.citedreference | Beutler E, Grabowski GA ( 2001 ) Gaucher disease. In: Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular basis of inherited disease (Scriver CR), New York: McGrawâ Hill, 3635 â 3668. | |
dc.identifier.citedreference | Brady RO, Kanfer JN, Bradley RM, Shapiro D ( 1966 ) Demonstration of a deficiency of glucocerebrosideâ cleaving enzyme in Gaucher’s disease. J. Clin. Invest., 45: 1112 â 1115, 10.1172/JCI105417 -->. | |
dc.identifier.citedreference | Charrow J, Andersson HC, Kaplan P, et al ( 2004 ) Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: consensus recommendations. J Pediatr., 144: 112 â 120, 10.1016/j.jpeds.2003.10.067 -->. | |
dc.identifier.citedreference | Cox TM, Aerts JM, Andria G, et al ( 2003 ) The role of the iminosugar Nâ butyldeoxynojirimycin (miglustat) in the management of type 1 (nonâ neuropathic) Gaucher disease: a position statement. J. Inherit. Metab. Dis., 26: 513 â 526, 10.1023/A:1025902113005 -->. | |
dc.identifier.citedreference | de Fost M, Hollack CEM, Groener JEM, et al ( 2006 ) Superior effects of highâ dose enzyme replacement therapy in type 1 Gaucher disease on bone marrow involvement and chitotriosidase levels: a 2â center retrospective analysis. Blood, 108: 830 â 835, 10.1182/blood‐2005‐12‐5072 -->. | |
dc.identifier.citedreference | Doering T, Holleran WM, Potratz A, Vielhaber G, Elias PM, Suzuki K, Sandhoff K ( 1999 ) Sphingolipid activator proteins are required for epidermal permeability barrier formation. J. Biol. Chem., 274: 11038 â 11045, 10.1074/jbc.274.16.11038 -->. | |
dc.identifier.citedreference | Elbein AD, Tropea JE, Mitchell M, Kaushal GP ( 1990 ) Kifunensine, a potent inhibitor of the glycoprotein processing mannosidase I. J. Biol. Chem., 265: 15599 â 15605. | |
dc.identifier.citedreference | Elstein D, Hollack C, Aerts JM, et al ( 2004 ) Sustained therapeutic effects of oral miglustat (Zavesca, Nâ butyldeoxynojirimycin, OGT 918) in type 1 Gaucher disease. J. Inherit. Metab. Dis., 27: 757 â 766, 10.1023/B:BOLI.0000045756.54006.17 -->. | |
dc.identifier.citedreference | Elstein D, Dwek A, Attias D, et al ( 2007 ) Oral maintenance clinical trial with miglustat for type 1 Gaucher disease: switch from or combination with intravenous enzyme replacement. Blood, 110: 2296 â 2301, 10.1182/blood‐2007‐02‐075960 -->. | |
dc.identifier.citedreference | Enquist IB, Nilsson E, Ooka A, et al ( 2006 ) Effective cell and gene therapy in a murine model of Gaucher disease. Proc. Natl. Acad. Sci. USA, 103: 13819 â 13824, 10.1073/pnas.0606016103 -->. | |
dc.identifier.citedreference | Futerman AH, Sussman JL, Horowitz M, Silman I, Zimran A ( 2004 ) New directions in the treatment of Gaucher disease. Trends Pharmacol Sci., 25: 147 â 151, 10.1016/j.tips.2004.01.004 -->. | |
dc.identifier.citedreference | Giraldo P, Latre P, Alfonso P, et al ( 2006 ) Shortâ term effect of miglustat in every day clinical use in treatmentâ naïve or previously treated patients with type 1 Gaucher disease. Hematologica, 91: 703 â 706. | |
dc.identifier.citedreference | Grabowski GA, Barton NW, Pastores G, et al ( 1995 ) Enzyme therapy in Type I Gaucher disease: comparative efficacy of mannoseâ terminated glucocerebrosidase from natural and recombinant sources. Ann. Int. Med., 122: 33 â 39. | |
dc.identifier.citedreference | Grabowski GA, Kacena K, Cole AJ, et al ( 2009 ) Doseâ response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1. Genet Med., 11: 92 â 100, 10.1097/GIM.0b013e31818e2c19 -->. | |
dc.identifier.citedreference | Hollak CE, Hughes D, van Schaik IN, Schwierin N, Bembi B ( 2009 ) Miglustat (Zavesca®) in type 1 Gaucher disease: 5â year results of a postâ authorisation safety surveillance programme. Pharmacoepidemiol. Drug Saf., 18: 770 â 777, 10.1002/pds.1779 -->. | |
dc.identifier.citedreference | Inokuchi J, Radin NS ( 1987 ) Preparation of the active isomer 1â phenylâ 2â decanoylâ aminoâ 3â morpholinoâ 1â propanol inhibitor of murine glucocerebrosidase synthase. J Lipid Chem., 28: 565 â 571. | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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