拉托齐内马布,一种用于治疗前性痴呆症的新型前素升高疗法
Michael Kurnellas1,2, Ananya Mitra3, Tina Schwabe3,4
1Alector, Inc., 131 Oyster Point Blvd, #600, South San Francisco, CA, 94080, USA. mpkurnellas@gmail.com.
Journal of translational medicine
|June 15, 2023
概括
拉托齐内马布是一种针对索尔提林的抗体,有效地增加了progranulin (PGRN) 水平. 这显示出前性痴呆症 (FTD-GRN) 和其他神经退行性疾病治疗的前途.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 前性痴呆症 (FTD-GRN) 与progranulin (PGRN) 基因 (GRN) 中的功能丧失突变有关.
- PGRN对于溶解体功能,免疫调节和神经元存活至关重要,索尔提林介导其溶解体运输.
- 目前的理解突出了索尔提林在PGRN降解中的作用及其作为治疗点的潜力.
研究的目的:
- 描述一种新型的人类单克隆抗体Latozinemab的特征,该抗体旨在向sortilin.
- 为了评估阻断FTD-GRN治疗的sortilin-PGRN相互作用的治疗潜力.
主要方法:
- 在体外研究中评估了latozinemab的作用机制.
- 在体内研究中使用了FTD-GRN的小鼠模型,非人类灵长类动物和1期人类临床试验.
- 评估了latozinemab的药理动力学,药理动力学和安全性.
主要成果:
- 在小鼠模型中,抗sortilin抗体使PGRN水平正常化,并挽救了行为缺陷.
- 在Cynomolgus子中,Latozinemab增加了血和脑脊液 (CSF) 的PGRN水平.
- 在人体试验中,latozinemab降低了sortilin,增加了血和CSF PGRN,并在无症状GRN突变载体中使PGRN正常化.
结论:
- 拉托齐内马布显示出有利的安全性概况,并有效地增加了PGRN水平.
- 这些研究结果支持Latozinemab用于FTD-GRN和其他神经退行性疾病的开发.
- 需要对提高PGRN的疗法进行进一步的研究.
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