Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis
Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis
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DOI：
10.1016/s0140-6736(00)02161-9
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发表时间：
2000-04-29
期刊：
影响因子：
168.9
通讯作者：
Zimran, A
中科院分区：
文献类型：
--
作者：
Cox, T;Lachmann, R;Zimran, A
背景目前戈谢病的治疗包括静脉注射葡萄糖脑苷脂酶以降解储存在溶酶体中的葡萄糖脑苷脂。降低葡糖脑苷脂的生物合成速率应减少该底物的生成。我们调查了OGT 918（N-丁基脱氧野尻霉素），葡萄糖基转移酶的抑制剂，作为一种新的口服治疗非神经元病Gaucher's diseases.Methods的安全性和有效性，我们招募，到一个为期1年的开放标签研究，28名成年人（7个以前的脾切除术）从四个国家Gaucher's转诊诊所，谁不能或不愿意接受酶治疗。我们通过计算机断层扫描或磁共振成像在基线和第6个月和第12个月测量肝脏和脾脏体积，每月测量生化和血液学变量，包括壳三糖苷酶活性（戈谢病活动的敏感标志物）。患者开始口服100 mg OGT 918，每日三次，结果基线肝脏体积为正常值的1.1-2.7倍，脾脏体积为正常值的5.1-24.8倍。在12个月时，平均肝脏和脾脏体积分别显著降低12%（95%CI 7.8-16.4）和19%（14.3-23.7）（均为p
Background Current treatment for Gaucher's disease involves administration of intravenous glucocerebrosidase to degrade glucocerebroside stored in lysosomes. Lowering the rate of biosynthesis of glucocerebroside should decrease accummulation of this substrate. We investigated the safety and efficacy of OGT 918 (N-butyldeoxynojirimycin), an inhibitor of glucosyltransferase, as a novel oral treatment for non-neuronopathic Gaucher's disease.Methods We recruited, into a 1-year open-label study, 28 adults (seven with previous splenectomies) from four national Gaucher's referral clinics, who were unable or unwilling to receive enzyme treatment. We measured liver and spleen volume by computed tomography or magnetic resonance imaging at baseline and at months 6 and 12, and biochemical and haematological variables monthly, including chitotriosidase activity (a sensitive marker of Gaucher's disease activity). Patients were started on 100 mg oral OGT 918 three times daily,Findings Baseline liver volumes were 1.1-2.7 times normal and spleen volumes 5.1-24.8 times normal. At 12 months, mean liver and spleen Volumes were significantly lowered by 12% (95% CI 7.8-16.4) and 19% (14.3-23.7), respectively (each p