Pastores Gregory M
a Departments of Neurology and Pediatrics, New York University School of Medicine, 403 East 34th Street, 2nd floor, New York, NY 10016, USA.
Expert Rev Endocrinol Metab. 2011 Jan;6(1):13-20. doi: 10.1586/eem.10.74.
Gaucher disease (GD) is an inherited disorder characterized by deficiency of the lysosomal enzyme glucocerebrosidase and the accumulation of an incompletely metabolized substrate (glucocerebroside) in cells of monocyte lineage. Clinical manifestations include anemia, thrombocytopenia, hepatosplenomegaly and bone disease; in a subset of patients with the neuropathic form, additional problems related to primary CNS involvement develop, resulting in a shortened lifespan. Velaglucerase alfa is a human recombinant formulation of glucocerebrosidase; in clinical trials it has been shown to be safe and effective in reversing the cardinal systemic features of GD. Prior to the introduction of velaglucerase alfa, enzyme replacement therapy with imiglucerase for GD type 1 (the non-neuronopathic form) had been established as the standard of care. Problems with imiglucerase supply have resulted in the increased use of velaglucerase alfa, through an expanded access program prior to regulatory approval (which was obtained in February 2010 in the USA and more recently in countries of the EU). Thus far, the therapeutic profile for velaglucerase alfa appears comparable to the historical data set for imiglucerase, although the reported rate of antibody formation against velaglucerase alfa is lower (1 vs 15%). In addition, in vitrostudies involving human macrophages have demonstrated a more rapid internalization of velaglucerase alfa. The long-term implications of these observations need to be established. Moreover, factors that will influence the choice of treatment agent in GD patients will need to be determined.
戈谢病（GD）是一种遗传性疾病，其特征是溶酶体酶葡萄糖脑苷脂酶缺乏，以及单核细胞系细胞中不完全代谢的底物（葡萄糖脑苷脂）蓄积。临床表现包括贫血、血小板减少、肝脾肿大和骨病；在一部分患有神经病变型的患者中，会出现与原发性中枢神经系统受累相关的其他问题，导致寿命缩短。维拉苷酶α是葡萄糖脑苷脂酶的一种重组人源制剂；在临床试验中，已证明其在逆转戈谢病的主要全身特征方面是安全有效的。在维拉苷酶α问世之前，1型戈谢病（非神经病变型）使用伊米苷酶进行酶替代治疗已成为标准治疗方法。由于伊米苷酶供应方面的问题，通过监管批准前的扩大使用计划（美国于2010年2月获得批准，欧盟国家最近也获得批准），维拉苷酶α的使用有所增加。到目前为止，维拉苷酶α的治疗效果似乎与伊米苷酶的历史数据集相当，尽管报道的针对维拉苷酶α的抗体形成率较低（1%对15%）。此外，涉及人类巨噬细胞的体外研究表明，维拉苷酶α的内化速度更快。这些观察结果的长期影响尚待确定。此外，还需要确定影响戈谢病患者治疗药物选择的因素。
