Safety and efficacy of recombinant human α-galactosidase a replacement therapy in Fabry's disease.
Safety and efficacy of recombinant human α-galactosidase a replacement therapy in Fabry's disease.
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DOI：
10.1056/nejm200107053450102
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发表时间：
2001-07-01
影响因子：
158.5
通讯作者：
Desnick, RJ
中科院分区：
文献类型：
--
作者：
Eng, CM;Guffon, N;Desnick, RJ
背景资料：法布里病，溶酶体α-半乳糖苷酶A缺乏，由神经酰胺和相关鞘糖脂的进行性积累引起。受影响的患者有微血管疾病的肾脏，心脏，和brain.Methods：我们评估的安全性和有效性的重组α-半乳糖苷酶A在一个多中心，随机，安慰剂对照，双盲研究的58例患者每2周治疗20周。此后，所有患者在开放标签扩展研究中接受重组α-半乳糖苷酶A。主要疗效终点是肾微血管内皮细胞沉积的神经酰胺三己糖苷被清除（降至正常或接近正常水平）的患者百分比。我们还评估了肌内膜和皮肤中神经酰胺三己糖苷微血管内皮沉积物的组织学清除率，以及疼痛水平和生活质量的变化。在双盲研究中，重组α-半乳糖苷酶A组的29名患者中有20名20周后，69%的患者没有神经酰胺三己糖苷微血管内皮沉积，而安慰剂组的29名患者中没有（P
Background: Fabry's disease, lysosomal alpha- galactosidase A deficiency, results from the progressive accumulation of globotriaosylceramide and related glycosphingolipids. Affected patients have microvascular disease of the kidneys, heart, and brain.Methods: We evaluated the safety and effectiveness of recombinant alpha -galactosidase A in a multicenter, randomized, placebo-controlled, double-blind study of 58 patients who were treated every 2 weeks for 20 weeks. Thereafter, all patients received recombinant alpha- galactosidase A in an open-label extension study. The primary efficacy end point was the percentage of patients in whom renal microvascular endothelial deposits of globotriaosylceramide were cleared (reduced to normal or near-normal levels). We also evaluated the histologic clearance of microvascular endothelial deposits of globotriaosylceramide in the endomyocardium and skin, as well as changes in the level of pain and the quality of life.Results: In the double-blind study, 20 of the 29 patients in the recombinant alpha -galactosidase A group (69 percent) had no microvascular endothelial deposits of globotriaosylceramide after 20 weeks, as compared with none of the 29 patients in the placebo group (P