Haddley K
Drugs Today (Barc). 2012 Aug;48(8):525-32. doi: 10.1358/dot.2012.48.8.1844808.
Gaucher's disease is a rare inherited inborn error of metabolism caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase, GBA. Glucocerebrosidase is involved in the metabolism of the lipid metabolism-derived substrate, glucocerebroside. Accumulation of glucocerebroside substrate in macrophages, as a result of loss of enzyme function, leads to the formation of Gaucher cells causing hypertrophy of the spleen and liver, hematological disorders, skeletal malformations and the neurological symptoms characteristic of Gaucher's disease. The disease is subdivided into three types that differ in their symptoms, severity and prognosis. Patients of any age can be affected but those of a younger age have a poor prognosis often dying in infancy. As a genetic disorder the incidence of the disease is variable on a global scale. Enzyme replacement therapy is the therapy of choice and has demonstrated good efficacy in treating the visceral and skeletal symptoms of Gaucher's disease. A cost-effective plant-cell-derived human recombinant glucocerebrosidase, taliglucerase alfa, has been developed that demonstrated a promising safety and efficacy profile in phase I clinical trials and is currently in phase III and IV trials for the treatment of pediatric and adult patients with Gaucher's disease.
戈谢病是一种罕见的遗传性先天性代谢缺陷病,由编码溶酶体酶葡萄糖脑苷脂酶(GBA)的基因突变引起。葡萄糖脑苷脂酶参与脂质代谢衍生底物葡萄糖脑苷脂的代谢。由于酶功能丧失,巨噬细胞中葡萄糖脑苷脂底物的积累导致戈谢细胞形成,进而引起脾脏和肝脏肿大、血液系统疾病、骨骼畸形以及戈谢病特有的神经症状。该疾病分为三种类型,症状、严重程度和预后各不相同。任何年龄的患者都可能受到影响,但年龄较小的患者预后较差,常在婴儿期死亡。作为一种遗传性疾病,该病在全球范围内的发病率各不相同。酶替代疗法是首选治疗方法,已证明在治疗戈谢病的内脏和骨骼症状方面具有良好疗效。一种具有成本效益的植物细胞衍生的人重组葡萄糖脑苷脂酶taliglucerase alfa已被开发出来,在I期临床试验中显示出有前景的安全性和疗效,目前正在进行III期和IV期试验,用于治疗戈谢病的儿童和成人患者。