Ohashi Toya, Iizuka Sayoko, Ida Hiroyuki, Eto Yoshikatsu
Department of Gene Therapy, Institute of DNA Medicine, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minatoku, Tokyo 105-8461, Japan.
Mol Genet Metab. 2008 Jul;94(3):313-8. doi: 10.1016/j.ymgme.2008.03.008. Epub 2008 May 5.
Fabry disease is a progressive, life-threatening lysosomal storage disorder which is characterized by deficient activity of the lysosomal enzyme alpha-galactosidase A. Studies have demonstrated that both enzyme preparations currently available for treatment of Fabry disease (i.e., agalsidase beta and agalsidase alpha) 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 alpha-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 alpha-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.
法布里病是一种进行性、危及生命的溶酶体贮积症，其特征是溶酶体酶α-半乳糖苷酶A的活性不足。研究表明，目前可用于治疗法布里病的两种酶制剂（即阿加糖酶β和阿加糖酶α）在大多数患者中引发免疫反应，这对尿中球三糖神经酰胺浓度的降低产生负面影响。在当前研究中，发现阿加糖酶β抗体与培养的法布里成纤维细胞和法布里小鼠组织中α-Gal A酶活性的抑制有关。然而，通过增加给予小鼠的酶剂量，可以克服抗体形成的负面影响。总之，抗体滴度和酶剂量在体内影响α-Gal A酶活性。需要进一步研究以调查抗体形成对接受酶替代疗法的抗体阳性法布里病患者的治疗反应有多大影响，以及是否可以通过调整酶剂量来克服负面影响。
