Human acid α-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II
Human acid α-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II
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DOI：
10.1093/hmg/8.12.2145
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发表时间：
1999-11-01
影响因子：
3.5
通讯作者：
Reuser, AJJ
中科院分区：
文献类型：
--
作者：
Bijvoet, AGA;Van Hirtum, H;Reuser, AJJ
庞贝氏病或 II 型糖原贮积病 (GSDII) 属于遗传性溶酶体贮积病家族。酸性α-葡萄糖苷酶的潜在缺乏会导致心脏、骨骼和平滑肌中糖原储存不同程度的严重程度。目前尚无针对这种致命疾病的治疗方法，但酶替代疗法的适用性正在研究中。为此，已在转基因兔奶中以工业规模生产重组人酸性α-葡萄糖苷酶。在本文中，我们证明了这种酶在 GSDII 敲除小鼠模型中的治疗效果。单剂量静脉注射后，除大脑外的所有组织均获得了酸性 α-葡萄糖苷酶缺乏症的完全纠正。酶给药。 6 个月内每周输注酶导致心脏、骨骼和平滑肌中溶酶体糖原的降解。尽管在治疗开始时疾病已处于晚期状态，但组织形态仍显着改善，该结果导致在患者中启动了酶替代疗法的 II 期临床试验。
Pompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency of acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal and smooth muscle. There is currently no treatment for this fatal disease, but the applicability of enzyme replacement therapy is under investigation. For this purpose, recombinant human acid alpha-glucosidase has been produced on an industrial scale in the milk of transgenic rabbits. In this paper we demonstrate the therapeutic effect of this enzyme in our knockout mouse model of GSDII. Full correction of acid alpha-glucosidase deficiency was obtained in all tissues except brain after a single dose of i.v. enzyme administration. Weekly enzyme infusions over a period of 6 months resulted in degradation of lysosomal glycogen in heart, skeletal and smooth muscle. The tissue morphology improved substantially despite the advanced state of disease at the start of treatment, The results have led to the start of a Phase II clinical trial of enzyme replacement therapy in patients.