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胰高血糖素样肽-1 类药物在帕金森病和阿尔茨海默病临床试验中显示出明确的保护作用:即将引发一场革命?

Glucagon-like peptide-1 class drugs show clear protective effects in Parkinson's and Alzheimer's disease clinical trials: A revolution in the making?

机构信息

Henan Academy of Innovations in Medical Science, Neurodegeneration Research Group, 451100 Xinzheng, Henan province, China.

出版信息

Neuropharmacology. 2024 Aug 1;253:109952. doi: 10.1016/j.neuropharm.2024.109952. Epub 2024 Apr 25.

Abstract

Parkinson's disease (PD) is a complex syndrome for which there is no disease-modifying treatment on the market. However, a group of drugs from the Glucagon-like peptide-1 (GLP-1) class have shown impressive improvements in clinical phase II trials. Exendin-4 (Bydureon), Liraglutide (Victoza, Saxenda) and Lixisenatide (Adlyxin), drugs that are on the market as treatments for diabetes, have shown clear effects in improving motor activity in patients with PD in phase II clinical trials. In addition, Liraglutide has shown improvement in cognition and brain shrinkage in a phase II trial in patients with Alzheimer disease (AD). Two phase III trials testing the GLP-1 drug semaglutide (Wegovy, Ozempic, Rybelsus) are ongoing. This perspective article will summarize the clinical results obtained so far in this novel research area. We are at a crossroads where GLP-1 class drugs are emerging as a new treatment strategy for PD and for AD. Newer drugs that have been designed to enter the brain easier are being developed already show improved effects in preclinical studies compared with the older GLP-1 class drugs that had been developed to treat diabetes. The future looks bright for new treatments for AD and PD.

摘要

帕金森病(PD)是一种复杂的综合征,目前市场上尚无针对该疾病的治疗方法。然而,一类来自胰高血糖素样肽-1(GLP-1)的药物在 II 期临床试验中显示出了显著的改善效果。Exendin-4(百达扬)、利拉鲁肽(诺和力、司美格鲁肽)和利西那肽(艾塞那肽)作为治疗糖尿病的药物,在 II 期临床试验中已明确显示出改善 PD 患者运动活动的效果。此外,利拉鲁肽在 AD 患者的 II 期临床试验中显示出认知功能改善和脑萎缩缩小的效果。两项正在进行的 III 期临床试验正在测试 GLP-1 药物司美格鲁肽(诺和泰、瑞格列汀、西格列汀)。本文将总结目前在这一新颖研究领域取得的临床结果。我们正处于一个转折点,GLP-1 类药物正在成为 PD 和 AD 的新治疗策略。为了更易进入大脑而设计的新型药物已经在临床前研究中显示出了改善效果,与旨在治疗糖尿病的更老一代 GLP-1 类药物相比,这些药物的效果得到了改善。AD 和 PD 的新治疗方法前景光明。

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