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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2296-2301. Prepublished online as a Blood First Edition Paper on July 3, 2007; DOI 10.1182/blood-2007-02-075960. This Article Full Text (PDF) All Versions of this Article: blood-2007-02-075960v1 110/7/2296    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Elstein, D. Articles by Zimran, A. Search for Related Content PubMed PubMed Citation Articles by Elstein, D. Articles by Zimran, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 21, 2007 Accepted June 21, 2007 Oral maintenance clinical trial with miglustat for type 1 Gaucher disease: switch from or combination with intravenous enzyme replacement Deborah Elstein*, Altoon Dweck, Drorit Attias, Irith Hadas-Halpern, Shoshana Zevin, Gheona Altarescu, Johannes F.M.G. Aerts, Sonja van Weely, and Ari Zimran Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel Department of Biochemistry, Academic Medical Center, Amsterdam, Netherlands * Corresponding author; email: elstein{at}szmc.org.il. Enzyme Replacement Therapy (ERT) with imiglucerase reduces hepatosplenomegaly and improves hematological parameters in Gaucher disease type 1 (GD1), within 6-24 months. Miglustat reduces organomegaly, improves hematological parameters and reverses bone-marrow infiltration. This trial evaluates miglustat in patients clinically stable on ERT. Tolerability of miglustat and imiglucerase, alone and in combination, pharmacokinetic profile, organ reduction, and chitotriosidase activity were assessed. Thirty-six patients stable on imiglucerase were randomized into this phase II, open-label trial. Statistically significant changes from baseline were assessed (paired t-test) on primary objectives with secondary analyses on biochemical and safety parameters. Liver and spleen volume were unchanged in switched patients. No significant differences were seen between groups regarding mean change in hemoglobin. Mean change in platelet counts was only significant between miglustat and imiglucerase groups (p=0.035). Chitotriosidase activity remained stable. In trial extension, clinical endpoints were generally maintained. Miglustat was well tolerated alone or in combination. Miglustat's safety profile was consistent with previous trials, moreover no new cases of peripheral neuropathy were observed. GD1 parameters were stable in most switched patients. Combination therapy did not show benefit. Findings suggest miglustat could be an effective maintenance therapy in stabilized patients with GD1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Douillard-Guilloux, N. Raben, S. Takikita, L. Batista, C. Caillaud, and E. Richard Modulation of glycogen synthesis by RNA interference: towards a new therapeutic approach for glycogenosis type II Hum. Mol. Genet., December 15, 2008; 17(24): 3876 - 3886. [Abstract] [Full Text] [PDF]

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