Efficacy of enzyme replacement therapy in Fabry disease.
Efficacy of enzyme replacement therapy in Fabry disease.
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DOI：
10.2174/1568016043356192
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发表时间：
2004-10-01
期刊：
影响因子：
--
通讯作者：
Burnier, M
中科院分区：
文献类型：
--
作者：
Barbey, F;Hayoz, D;Burnier, M
酶替代疗法最近被引入治疗法布里病，这是一种罕见的X连锁溶酶体储存障碍。这种疾病的发生是由于α-半乳糖苷酶A活性不足，导致球状三糖神经酰胺在多个器官和组织中进行性积聚。这种疾病的肾脏、心脏和脑血管表现导致半合子男性和杂合子女性过早死亡。本文概述了Fabry病的临床表现、症状和诊断，以及两种可用的酶替代疗法--琼脂糖苷酶α和琼脂糖苷酶β的研究进展。在人类细胞系和中国仓鼠卵巢细胞中分别产生琼脂糖苷酶α和琼脂糖苷酶β，导致产物具有与天然人类酶相同的氨基酸序列，但具有不同的糖基化模式。正确的翻译后糖基化对于基因工程蛋白疗法的药代动力学、生物分布、临床疗效和耐受性是重要的。糖基化的差异可能影响免疫原性和甘露糖-6-磷酸受体介导的给药酶的细胞内化，这可能解释了已报道的琼脂糖苷酶α和β在剂量、临床效果和安全性方面的差异。
Enzyme replacement therapy has recently been introduced to treat Fabry disease, a rare X-linked lysosomal storage disorder. The disease occurs due to deficient activity of alpha-galactosidase A, leading to progressive accumulation of globotriaosylceramide in multiple organs and tissues. Renal, cardiac and cerebrovascular manifestations of the disease result in premature death in both hemizygous males and heterozygous females. This paper outlines the clinical signs, symptoms and diagnosis of Fabry disease, and the development of the two available enzyme replacement therapies -- agalsidase alfa and agalsidase beta. Agalsidase alfa and agalsidase beta are produced in a human cell line and in Chinese hamster ovary cells, respectively, resulting in products with the same amino acid sequence as the native human enzyme, but with different patterns of glycosylation. Correct post-translational glycosylation is important in terms of the pharmacokinetics, biodistribution, clinical efficacy and tolerability of genetically engineered protein therapeutics. Differences in glycosylation, which may affect immunogenicity and mannose-6-phosphate receptor-mediated cellular internalisation of administered enzyme, possibly account for the differences in dosing, clinical effects and safety profiles reported for agalsidase alfa and agalsidase beta.