Enzyme replacement therapy in a feline model of Maroteaux-Lamy syndrome
Enzyme replacement therapy in a feline model of Maroteaux-Lamy syndrome
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DOI：
10.1172/jci118617
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发表时间：
1996-04-15
影响因子：
15.9
通讯作者：
Hopwood, JJ
中科院分区：
文献类型：
--
作者：
Crawley, AC;Brooks, DA;Hopwood, JJ
我们报告的研究表明，酶替代疗法将显着减少 Maroteaux-Lamy 综合征（VI 型粘多糖贮积症，MPS VI）患者的疾病进展和组织病理学。 MPS VI 猫科动物模型用于评估三种形式的重组人 N-乙酰半乳糖胺-4-硫酸酯酶（rh4S，EC 3.1.6.1）的组织分布和临床功效。静脉注射的 rh4S 迅速从循环中清除。大多数 rh4S 分布于肝脏，但在大多数其他组织中也检测到。组织半衰期类似于2-4天。三只 MPS VI 猫定期静脉输注 rh4S 长达 20 个月，显示库普弗细胞和结缔组织中的储存空泡不同程度减少，但软骨细胞仍呈空泡状态。两只在骨骼成熟之前开始治疗的 MPS VI 猫的椎骨骨矿物质体积得到改善，骨体积的增加似乎与较早开始治疗的年龄相关。一只猫对治疗的反应表现出更大的活动能力。
We report studies that suggest enzyme replacement therapy will result in a significant reduction in disease progression and tissue pathology in patients with Maroteaux-Lamy syndrome (Mucopolysaccharidosis type VI, MPS VI). A feline model for MPS VI was used to evaluate tissue distribution and clinical efficacy of three forms of recombinant human N-acetylgalactosamine-4-sulfatase (rh4S, EC 3.1.6.1). Intravenously administered rh4S was rapidly cleared from circulation. The majority of rh4S was distributed to liver, but was also detected in most other tissues. Tissue half-life was similar to 2-4 d. Three MPS VI cats given regular intravenous infusions of rh4S for up to 20 mo showed variable reduction of storage vacuoles in Kupffer cells and connective tissues, however cartilage chondrocytes remained vacuolated. Vertebral bone mineral volume was improved in two MPS VI cats in which therapy was initiated before skeletal maturity, and increased bone volume appeared to correlate with earlier age of onset of therapy. One cat showed greater mobility in response to therapy.