Pastores Gregory M
New York University School of Medicine, Departments of Neurology and Pediatrics, New York, NY 10016, USA.
Curr Opin Investig Drugs. 2010 Apr;11(4):472-8.
Gaucher disease (GD) is caused by a deficiency of the lysosomal enzyme glucocerebrosidase, which results in the accumulation of its substrate, glucocerebroside, in macrophages. This excess in lipid storage within macrophages (subsequently recognized as Gaucher cells) leads to the development of disease, which presents clinical features including anemia, thrombocytopenia and hepatosplenomegaly, and can also lead to the development of neurological problems or bone disease. Velaglucerase alfa is a gene-activated human recombinant glucocerebrosidase being developed by Shire Human Genetic Therapies Inc as an enzyme replacement therapy for type 1 GD. In vitro, velaglucerase alfa was internalized by human macrophages more rapidly than imiglucerase, which has been the sole standard of care for GD for over 15 years. Clinical trials in patients with GD demonstrated that the safety and efficacy of velaglucerase alfa appeared to be comparable with historical imiglucerase data, although head-to-head data were unavailable. Recent problems with the production of imiglucerase led to the unanticipated introduction of velaglucerase alfa to patients with GD through a pre-approval expanded access protocol. Whether this will prove beneficial, in terms of uptake and prescribing of the enzyme, remains to be seen in a market dominated by imiglucerase.
戈谢病（GD）是由溶酶体酶葡萄糖脑苷脂酶缺乏引起的，这导致其底物葡萄糖脑苷脂在巨噬细胞中蓄积。巨噬细胞内脂质储存过量（随后被识别为戈谢细胞）会引发疾病，其临床特征包括贫血、血小板减少和肝脾肿大，还可能导致神经问题或骨骼疾病的发生。维拉苷酶α是夏尔人类基因治疗公司研发的一种基因激活型人重组葡萄糖脑苷脂酶，作为1型GD的酶替代疗法。在体外，维拉苷酶α被人类巨噬细胞内化的速度比伊米苷酶更快，在超过15年的时间里，伊米苷酶一直是GD唯一的标准治疗药物。GD患者的临床试验表明，尽管缺乏直接对比数据，但维拉苷酶α的安全性和有效性似乎与伊米苷酶的历史数据相当。最近伊米苷酶生产出现的问题导致通过预先批准的扩大使用方案意外地将维拉苷酶α用于GD患者。在由伊米苷酶主导的市场中，这在酶的使用和处方方面是否会被证明有益，仍有待观察。
