表征的化学改性植物细胞培养表达人类alpha-Galactosidase-A酶Fabry疾病的治疗。

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Kizhner T, Azulay Y, Hainrichson M, Tekoah Y, Arvatz G,舒曼,Ruderfer我有D, Shaaltiel Y

表征的化学改性植物细胞培养表达人类alpha-Galactosidase-A酶Fabry疾病的治疗。

摩尔麝猫金属底座。2015年2月,114 (2):259 - 67。doi: 10.1016 / j.ymgme.2014.08.002。Epub 2014 8月10。

PubMed ID
25155442 (在PubMed
]
文摘

Fabry疾病的x染色体隐性障碍引起的溶酶体酶alpha-Galactosidase-A功能的丧失。虽然两个酶替代疗法(艺)是商用,他们可能不会有效地扭转一些Fabry病理学。插件可以- 102是一种新型酶的治疗Fabry疾病表达BY2烟草细胞培养。插件可以- 102是化学改性,导致交联homo-dimer。我们有特点的体外和体内性质插件可以- 102和相比alpha-Galactosidase-A酶产生的结果与两个商业。- 102结果表明,插件可以延长体外稳定等离子体,1 h孵化后保留30%活动而完整的商业酶失活。- 102 lysosomal-like条件下插件可以保持80%以上活动后10天的孵化,而商业酶失去活性后2天。药代动力学- 102的插件可以以男性Fabry老鼠显示增加10倍t1/2相比,老鼠(581分钟)批准的药物。酶有显著不同的动力学参数可用的替代艺(p值< 0.05,方差分析的一种方法),尽管这些差异并不意味着任何重要的生化变化。插件可以- 102是人类Fabry成纤维细胞实验为主。 The repeat administration of the enzyme to Fabry mice caused significant reduction (p-value<0.05) of Gb3 in various tissues (the measured residual content was 64% in kidney, liver was cleaned, 23% in heart, 5.7% in skin and 16.2% in spleen). PRX-102 has a relatively simple glycosylation pattern, characteristic to plants, having mainly tri-mannose structures with the addition of either alpha(1-3)-linked fucose or beta(1-2)-linked xylose, or both, in addition to various high mannose structures, while agalsidase beta has a mixture of sialylated glycans in addition to high mannose structures. This study concludes that PRX-102 is equivalent in functionality to the current ERTs available, with superior stability and prolonged circulatory half-life. Therefore we propose that PRX-102 is a promising alternative for treatment of Fabry disease.

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药物
药物靶点
药物 目标 类 生物 药理作用 行动
Pegunigalsidase阿尔法 Globotriaosylceramide 集团 人类
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