Tralesinidase阿尔法酶替代疗法可以防止疾病表现在犬模型的黏多糖病类型希望。
文章的细节
-
引用
复制到剪贴板 -
Ellinwood NM,情人节BN,赫斯,Jens JK Snella EM,贾米尔M, Hostetter SJ,杰弗瑞ND,史密斯JD,米尔曼圣,帕森斯RL,屁股太,钱德拉年代,Egeland MT,阿西斯AB, Nelvagal人力资源,库珀JD, Nestrasil我,穆勒英航Labounek R,保尔森,金属小球H,刘XY,周H,劳伦斯·R·克劳福德,格罗弗,Cherala G, Melton AC, Cherukuri, Vuillemenot BR,等待JCM,奥尼尔,Pinkstaff J, Kovalchin J, Zanelli E, McCullagh E
Tralesinidase阿尔法酶替代疗法可以防止疾病表现在犬模型的黏多糖病类型希望。
J Exp其他杂志》2022年9月,382 (3):277 - 286。doi: 10.1124 / jpet.122.001119。Epub 2022年6月18日。
- PubMed ID
-
35717448 (在PubMed]
- 文摘
-
希望具有黏多糖病类型(议员希望;礼宾部主管综合症B;人类# 252920)是一个致命的、儿科、神经性、常染色体隐性和溶酶体存储疾病没有批准的疗法。患者缺乏N-acetyl-alpha-glucosaminidase的活动(NAGLU;EC 3.2.150),正常的溶酶体降解所需的糖胺聚糖硫酸乙酰肝素(HS)。Tralesinidase阿尔法(TA)融合蛋白组成的重组人类NAGLU和修改后的人类胰岛素样生长因子2,在发展一种酶替代疗法是通过intracerebroventricular管理(ICV)注入,从而绕过血脑屏障。先前的研究已经证实了ICV注入导致TA的广泛分布在小鼠和非人灵长类动物的大脑。我们评估了长期的耐受性、药理学和临床疗效的助教在犬模型的议员希望在20个月的研究。长期管理助教耐受性良好,相比之下,政府车辆。助教是广泛分布在大脑区域,在后续确认8周药动学/药效学研究。 MPS IIIB dogs treated for up to 20 months had near-normal levels of HS and nonreducing ends of HS in cerebrospinal fluid and central nervous system (CNS) tissues. TA-treated MPS IIIB dogs performed better on cognitive tests and had improved CNS pathology and decreased cerebellar volume loss relative to vehicle-treated MPS IIIB dogs. These findings demonstrate the ability of TA to prevent or limit the biochemical, pathologic, and cognitive manifestations of canine MPS IIIB disease, thus providing support of its potential long-term tolerability and efficacy in MPS IIIB subjects. SIGNIFICANCE STATEMENT: This work illustrates the efficacy and tolerability of tralesinidase alfa as a potential therapeutic for patients with mucopolysaccharidosis type IIIB (MPS IIIB) by documenting that administration to the central nervous system of MPS IIIB dogs prevents the accumulation of disease-associated glycosaminoglycans in lysosomes, hepatomegaly, cerebellar atrophy, and cognitive decline.
beplay体育安全吗DrugBank数据引用了这篇文章
- 药物