Long-Term Intravenous Treatment of Pompe Disease With Recombinant Human -Glucosidase From Milk
Long-Term Intravenous Treatment of Pompe Disease With Recombinant Human -Glucosidase From Milk
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用牛奶中的重组人葡萄糖苷酶长期静脉治疗庞贝病
DOI：
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
A. T. Ploeg
中科院分区：
文献类型：
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作者：
J. M. P. V. D. Hout;Joep H. J. Kamphoven;L. Winkel;W. F. Arts;J. B. C. Klerk;M. C. B. Loonen;A. Vulto;A. Cromme;N. Weisglas‐Kuperus;W. Hop;Hans van Hirtum;O. Diggelen;M. Boer;M. Kroos;P. Doorn;E. Voort;B. Sibbles;Emiel J. J. M. Van Corven;J. Brakenhoff;J. Hove;J. Smeitink;G. Jong;A. Reuser;A. T. Ploeg
客观的。最近的报告警告说，全球细胞培养能力不足以满足人类蛋白质药物日益增长的需求。用转基因动物的奶生产是一个有吸引力的替代方案。每年可以以相对较低的成本获得公斤数量的产品，即使是兔子等小动物也是如此。我们测试了兔奶中的重组人葡萄糖苷酶（rhAGLU）治疗溶酶体贮积症庞贝病的长期安全性和有效性。该疾病的发生频率估计为四万分之一，被指定为孤儿病。典型的婴儿型导致中位年龄为 6 至 8 个月时死亡，并通过缺乏 β-葡萄糖苷酶活性和 β-葡萄糖苷酶基因中存在完全有害的突变来诊断。心脏肥大是其特征性表现。肌肉力量的丧失会阻碍婴儿实现坐、站立和行走等发育里程碑。该疾病的较轻形式与不太严重的突变和β-葡萄糖苷酶的部分缺乏有关。方法。 1999年初，4名危重婴儿庞贝病患者（2.5-8个月大）被纳入一项单中心开放标签研究，并以15至40 mg/kg/周的剂量静脉注射rhAGLU治疗。结果。患者的基因型与最严重的庞贝氏病一致。额外的分子分析未能在 4 名患者中的 3 名中检测到加工形式的 β-葡萄糖苷酶（95、76 和 70 kDa），并且在第四名患者（患者 1）中仅发现微量的 95-kDa 生物合成中间体形式。采用更灵敏的检测方法，35S-蛋氨酸掺入-
Objective. Recent reports warn that the worldwide cell culture capacity is insufficient to fulfill the increasing demand for human protein drugs. Produc- tion in milk of transgenic animals is an attractive alter- native. Kilogram quantities of product per year can be obtained at relatively low costs, even in small animals such as rabbits. We tested the long-term safety and effi- cacy of recombinant human -glucosidase (rhAGLU) from rabbit milk for the treatment of the lysosomal stor- age disorder Pompe disease. The disease occurs with an estimated frequency of 1 in 40 000 and is designated as orphan disease. The classic infantile form leads to death at a median age of 6 to 8 months and is diagnosed by absence of -glucosidase activity and presence of fully deleterious mutations in the -glucosidase gene. Cardiac hypertrophy is characteristically present. Loss of muscle strength prevents infants from achieving developmental milestones such as sitting, standing, and walking. Milder forms of the disease are associated with less severe mu- tations and partial deficiency of -glucosidase. Methods. In the beginning of 1999, 4 critically ill pa- tients with infantile Pompe disease (2.5- 8 months of age) were enrolled in a single-center open-label study and treated intravenously with rhAGLU in a dose of 15 to 40 mg/kg/week. Results. Genotypes of patients were consistent with the most severe form of Pompe disease. Additional mo- lecular analysis failed to detect processed forms of -glu- cosidase (95, 76, and 70 kDa) in 3 of the 4 patients and revealed only a trace amount of the 95-kDa biosynthetic intermediate form in the fourth (patient 1). With the more sensitive detection method, 35S-methionine incorpora-
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人酸性α-葡萄糖苷酶的 cDNA 和 5 侧翼区域的序列、5 非翻译前导序列中内含子的检测、18 bp 多态性的定义以及与先前 cDNA 和氨基酸序列的差异。
影响因子：
3.1
作者：
Martiniuk,F;Mehler,M;Tzall,S;Meredith,G;Hirschhorn,R
通讯作者：
Hirschhorn,R
在酸性α-葡萄糖苷酶突变体（Pompe）小鼠中，储存在骨骼中但不在心肌中的糖原对转基因编码的人类酶具有高度抵抗力。
DOI：
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发表时间：
2002
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
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作者：
Raben,Nina;Jatkar,Tejas;Lee,Alicia;Lu,Nina;Dwivedi,Sunita;Nagaraju,Kanneboyina;Plotz,PaulH
通讯作者：
Plotz,PaulH
影响因子：
9.8
作者：
Eng, CM;Banikazemi, M;Desnick, RJ
通讯作者：
Desnick, RJ
影响因子：
2.8
作者：
DEVEREUX, RB;CASALE, PN;ALONSO, DR
通讯作者：
ALONSO, DR