{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:49:10Z","timestamp":1790689750035,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,3,25]],"date-time":"2010-03-25T00:00:00Z","timestamp":1269475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gaucher disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (acid \u03b2\u2010glucosidase), with consequent cellular accumulation of glucosylceramide (GL\u20101). 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 GL\u20101 storage in the liver, spleen, and lung of 3\u2010month\u2010old Gaucher mice. SRT using a novel inhibitor of glucosylceramide synthase (Genz\u2010112638) was also effective, albeit to a lesser degree than ERT. Animals administered recombinant glucocerebrosidase and then Genz\u2010112638 showed the lowest levels of GL\u20101 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 GL\u20101 in the affected organs. Hence, in patients whose disease has been stabilized by intravenously administered recombinant glucocerebrosidase, orally administered SRT with Genz\u2010112638 could potentially be used as a convenient maintenance therapy. In patients na\u00efve to treatment, ERT followed by SRT could potentially accelerate clearance of the offending substrate.<\/jats:p>","DOI":"10.1007\/s10545-010-9072-z","type":"journal-article","created":{"date-parts":[[2010,3,24]],"date-time":"2010-03-24T11:16:16Z","timestamp":1269429376000},"page":"281-289","source":"Crossref","is-referenced-by-count":41,"title":["Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy"],"prefix":"10.1002","volume":"33","author":[{"given":"John","family":"Marshall","sequence":"first","affiliation":[{"name":"Genzyme Corporation 49 New York Avenue Framingham MA 01701\u20109322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry Anne","family":"McEachern","sequence":"additional","affiliation":[{"name":"Genzyme Corporation 49 New York Avenue Framingham MA 01701\u20109322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Lien","family":"Chuang","sequence":"additional","affiliation":[{"name":"Genzyme Corporation 49 New York Avenue Framingham MA 01701\u20109322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hutto","sequence":"additional","affiliation":[{"name":"Genzyme Corporation 49 New York Avenue Framingham MA 01701\u20109322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig S.","family":"Siegel","sequence":"additional","affiliation":[{"name":"Genzyme Corporation 49 New York Avenue Framingham MA 01701\u20109322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Shayman","sequence":"additional","affiliation":[{"name":"University of Michigan Ann Arbor MI 48103 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg A.","family":"Grabowski","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Research Foundation Cincinnati OH 45229 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald K.","family":"Scheule","sequence":"additional","affiliation":[{"name":"Genzyme Corporation 49 New York Avenue Framingham MA 01701\u20109322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane P.","family":"Copeland","sequence":"additional","affiliation":[{"name":"Genzyme Corporation 49 New York Avenue Framingham MA 01701\u20109322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seng H.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Genzyme Corporation 49 New York Avenue Framingham MA 01701\u20109322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,3,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1619"},{"key":"e_1_2_6_3_1","first-page":"3635","volume-title":"The metabolic and molecular basis of inherited disease (Scriver CR)","author":"Beutler E","year":"2001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI105417"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2003.10.067"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025902113005"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-12-5072"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.16.11038"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)55439-9"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BOLI.0000045756.54006.17"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-02-075960"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606016103"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2004.01.004"},{"key":"e_1_2_6_14_1","first-page":"703","article-title":"Short\u2010term effect of miglustat in every day clinical use in treatment\u2010na\u00efve or previously treated patients with type 1 Gaucher disease","volume":"91","author":"Giraldo P","year":"2006","journal-title":"Hematologica"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-122-1-199501010-00005"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31818e2c19"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1779"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)38673-9"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.1.327"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1725"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","unstructured":"KishnaniPSDiRoccoMKaplanPet alA 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 1Mol. 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