Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease D. ELSTEIN 1 , C. HOLLAK 2 , J. M. F. G. AERTS 2 , S. VAN WEELY 2 , M. MAAS 2 , T. M. COX 3 , R. H. LACHMANN 3 , M. HREBICEK 4 , F. M. PLATT 5 , T. D. BUTTERS 5 , R. A. DWEK 5 , and A. ZIMRAN 1 * 1 Shaare Zedek Medical Centre, Jerusalem, Israel; 2 Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; 3 Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK; 4 Institute of Inherited Metabolic Disorders, Prague, Czech Republic; 5 Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, UK *Correspondence: Gaucher Clinic, Shaare Zedek Medical Centre, PO Box 3235, Jerusalem 91031, Israel. E-mail: zimran@md.huji.ac.il MS received 25.05.04 Accepted 21.06.04 Summary: It has been shown that treatment with miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) improves key clinical features of type I Gaucherdiseaseafter1yearoftreatment.Thisstudyreportslonger-termef¢cacy and safety data. Patients who had completed 12 months of treatment with open-label miglustat (100^300mg three times daily) were enrolled to continue with therapy in an extension study. Data are presented up to month 36. Liver and spleen volumes measured by CT or MRI were scheduled every 6 months. Biochemical and haematological parameters, including chitotriosidase activity (asensitivemarkerofGaucherdiseaseactivity)weremonitoredevery3months. Safetydatawerealsocollectedevery3months.Eighteenof22eligiblepatients atfourcentresenteredtheextensionphaseand14ofthesecompleted36months oftreatmentwithmiglustat.After36months,therewerestatisticallysigni¢cant improvementsinallmajoref¢cacyendpoints.Liverandspleenorganvolumes werereducedby18%and30%,respectively.Inpatientswhosehaemoglobinvalue hadbeenbelow11.5g/dlatbaseline,meanhaemoglobinincreasedprogressively frombaselineby0.55g/dlatmonth12(NS),1.28g/dlatmonth24( p ¼ 0.007), and 1.30g/dl at month 36 (p ¼ 0.013). The mean platelet count at month 36 increased from baseline by 2210 9 /L. No new cases of peripheral neuropathy occurredsincepreviouslyreported.Diarrhoeaandweightloss,whichwerefre- quently reported during the initial 12-month study, decreased in magnitude andprevalenceduringthesecondandthirdyears.Patientstreatedwithmiglustat for3yearsshowsigni¢cantimprovementsinorganvolumesandhaematological J.Inherit.Metab.Dis. 27(2004)757^766 # SSIEMandKluwerAcademicPublishers.PrintedintheNetherlands 757