药物开发 药物开发
Tiffini Voss1, Paulette Triglia1, Yan G Ni2
1PassageBio, Philadelphia, PA, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 26, 2025
概括
PBFT02基因疗法通过增加进激素水平,对前性痴呆症 (FTD) 呈现有前途的效果. 早期的数据表明,FTD-GRN可能成为一次性治疗,支持进一步的临床开发.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 药理学 药理学是指药理学的学科.
背景情况:
- 前性痴呆症 (FTD) 占25-30%的病例,由于C9orf72,GRN或MAPT的自体主导突变.
- 目前对于FTD,包括FTD-GRN.目前还没有疾病修饰性治疗方法.
- PBFT02是一种针对FTD-GRN和FTD-C9orf72.72的试验性疗法.
研究的目的:
- 评估PBFT02基因疗法的安全性和耐受性,进行首次在人体临床试验 (upliFT-D).
- 评估目标参与 (progranulin/PGRN),生物活性和疾病进展的生物标志物.
- 研究PBFT02作为FTD的一次性疾病修饰治疗的潜力.
主要方法:
- PBFT02是一种传递人类GRN基因的AAV1载体,通过内注射 (ICM) 进行注射.
- 升高FT-D试验 (NCT04747431) 招募了顺序FTD-GRN和FTD-C9orf72队列.
- 安全性,耐受性和生物标志物数据 (CSF PGRN,血NfL) 收集在2年期间,延长至3年.
主要成果:
- 在所有参与者中,PBFT02显著增加了CSF PGRN水平,从3 ng/mL到13-34 ng/mL在6-12个月.
- CSF PGRN的增加是稳定的,持续长达18个月.
- 血NfL水平保持稳定,与自然历史数据相比,其变化率较低. 两名参与者经历了SAE (肝毒性,静脉鼻血栓).
结论:
- 来自upliFT-D试验的临时数据表明PBFT02是FTD-GRN的潜在一次性治疗方法.
- PBFT02显示出有前途的安全性和生物标志物参与.
- 根据这些早期发现,对FTD进行PBFT02的进一步临床开发是有必要的.
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