开辟了拉帕素作为日经保护剂的临床使用的道路
Adam R Konopka1,2,3, Dudley W Lamming4,5,
1Division of Geriatrics, Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA. akonopka@medicine.wisc.edu.
GeroScience
|October 6, 2023
概括
拉巴胺通过抑制mtORC1来促进健康衰老,但副作用可能来自mtORC2的抑制. 临床试验正在研究间歇性剂量,以更安全,更有效地预防与年龄相关的疾病.
科学领域:
- 老年学和衰老研究研究.
- 分子生物学和药理学 分子生物学和药理学
背景情况:
- 在模型系统中,一种mTORC1抑制剂Rapamycin可以延长寿命,并延迟与年龄相关的疾病.
- 担心拉巴胺的副作用 (免疫抑制,代谢干扰) 限制了人类的翻译.
- 一个模型表明,副作用与非目标mTORC2抑制有关,与mTORC1抑制不同.
研究的目的:
- 探索安全地转化拉巴胺素对人类健康衰老的好处的策略.
- 为了研究间歇性剂量或选择性mTORC1抑制的替代性Rapalogs.
- 为了解决拉帕米辛在与年龄相关的疾病中的安全性,药理动力学,药理动力学和疗效问题.
主要方法:
- 突出正在进行和即将进行的临床试验.
- 专注于早期阶段的研究来评估安全性和有效性.
- 评估与衰老相关的临床导向结果.
主要成果:
- 目前正在进行的试验旨在确定最佳的剂量表和长期的人类疗效.
- 早期阶段的研究将提供关于安全性,药理动力学和药理动力学的数据.
- 结果将为更大的第三阶段临床试验的设计提供信息.
结论:
- 通过拉帕米辛或拉帕洛格的选择性mTORC1抑制具有治疗和预防与年龄有关的疾病的潜力.
- 间歇剂量可能提供治疗窗口,以最大限度地提高益处,同时最大限度地减少副作用.
- 临床试验至关重要,以确定拉帕素对人类衰老的安全性和有效性.
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