Reduced α-Gal A enzyme activity in Fabry fibroblast cells and Fabry mice tissues induced by serum from antibody positive patients with Fabry disease

被引：48

作者：

Ohashi, Toya ^{[1
,2
]}

Iizuka, Sayoko ^{[1
]}

Ida, Hiroyuki ^{[1
,2
]}

Eto, Yoshikatsu ^{[1
,2
]}

机构：

[1] Jikei Univ, Sch Med, Inst DNA Med, Dept Gene Therapy,Minato Ku, Tokyo 1058461, Japan

[2] Jikei Univ, Sch Med, Dept Pediat, Tokyo 1058461, Japan

来源：

MOLECULAR GENETICS AND METABOLISM | 2008年 / 94卷 / 03期

关键词：

Fabry disease; alpha-galactosidase a; antibody; agalsidase beta; neutralizing activity; dose;

D O I：

10.1016/j.ymgme.2008.03.008

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Fabry disease is a progressive, life-threatening lysosomal storage disorder which is characterized by deficient activity of the lysosomal enzyme a-galactosidase A. Studies have demonstrated that both enzyme preparations currently available for treatment of Fabry disease (i.e., agalsidase beta and agalsidase alfa) elicit immune responses in the majority of patients which negatively influences the reduction of urinary globotriaosylceramide concentration. In the current study, agalsidase beta antibodies were found to be associated with inhibition of a-Gal A enzyme activity in cultured Fabry fibroblast and tissues from Fabry mice. However, the negative effect of antibody formation could be overcome by increasing the dose of enzyme administered to mice. In conclusion, antibody titers and the dose of enzyme influenced a-Gal A enzyme activities in vivo. Further studies are required to investigate to what extend antibody formation impacts on therapeutic responses in antibody positive Fabry patients receiving enzyme replacement therapy and if negative effects can be overcome by adjusting the dose of enzyme. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：313 / 318

页数：6

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