Recombinant human acid α-glucosidase enzyme therapy for infantile glycogen storage disease type II:: Results of a phase I/II clinical trial
Recombinant human acid α-glucosidase enzyme therapy for infantile glycogen storage disease type II:: Results of a phase I/II clinical trial
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DOI：
10.1097/00125817-200103000-00008
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发表时间：
2001-03-01
影响因子：
8.8
通讯作者：
Chen, YT
中科院分区：
文献类型：
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作者：
Amalfitano, A;Bengur, AR;Chen, YT
目的：婴儿糖原累积病II型（GSD-II）是由酸性α-葡萄糖苷酶（GAA）缺乏引起的一种致死性遗传性肌肉疾病。本研究的目的是研究重组人GAA（rhGAA）酶治疗这种致命性疾病的安全性和有效性。研究方法：该研究设计为一项I/II期、开放标签、rhGAA单次给药研究，每周两次静脉输注3例婴儿GSD-II。本研究中使用的rhGAA是从过量生产GAA的基因工程中国仓鼠卵巢（CHO）细胞中纯化的。在1年的试验期间，评价了rhGAA对心脏、肺、神经和运动功能的不良反应和疗效。评估的主要终点是1岁时的无心力衰竭生存率。这是基于历史对照数据，几乎所有患者在1岁时死于心力衰竭。结果：超过250次输注的结果显示rhGAA通常耐受良好。在所有三名婴儿中观察到心脏大小稳定减小，并且维持正常的心脏功能超过1年，这些婴儿已经过了1岁的临界年龄（目前为16、18和22个月大），并且继续具有正常的心脏功能。还观察到骨骼肌功能改善; 1例患者显示出显著改善，目前肌肉张力和力量正常，神经系统和丹佛发育评估正常。肌肉活组织检查证实，在该患者中，rhGAA治疗后糖原累积显著减少。结论：这是来自CHO细胞的重组人GAA的I/II期首次研究，表明rhGAA能够改善婴儿GSD-II患者的心脏和骨骼肌功能。需要进一步的研究来评估这种疗法的整体潜力。
Purpose: Infantile glycogen storage disease type II (GSD-II) is a fatal genetic muscle disorder caused by deficiency of acid a-glucosidase (GAA). The purpose of this study was to investigate the safety and efficacy of recombinant human GAA (rhGAA) enzyme therapy for this fatal disorder. Methods: The study was designed as a phase I/II, open-label, single-dose study of rhGAA infused intravenously twice weekly in three infants with infantile GSD-II. rhGAA used in this study was purified from genetically engineered Chinese hamster ovary (CHO) cells overproducing GAA. Adverse effects and efficacy of rhGAA upon cardiac, pulmonary, neurologic, and motor functions were evaluated during 1 year of the trial period. The primary end point assessed was heart failure-free survival at 1 year of age. This was based on historical control data that virtually all patients died of cardiac failure by 1 year of age. Results: The results of more than 250 infusions showed that rhGAA was generally well tolerated. Steady decreases in heart size and maintenance of normal cardiac function for more than 1 year were observed in all three infants, These infants have well passed the critical age of 1 year (currently 16, 18, and 22 months old) and continue to have normal cardiac function. Improvements of skeletal muscle functions were also noted; one patient showed marked improvement and currently has normal muscle tone and strength as well as normal neurologic and Denver developmental evaluations. Muscle biopsies confirmed that dramatic reductions in glycogen accumulation had occurred after rhGAA treatment in this patient. Conclusions: This phase I/II first study of recombinant human GAA derived from CHO cells showed that rhGAA is capable of improving cardiac and skeletal muscle functions in infantile GSD-II patients. Further study will be needed to assess the overall potential of this therapy.