阿尔茨海默病的疾病修饰疗法:临床试验进展与机遇。

IF 12.5 1区 医学 Q1 CELL BIOLOGY
Yujie Zhang , Jie Chen , Yanru Li , Bin Jiao , Shilin Luo
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引用次数: 0

摘要

美国食品和药物管理局(FDA)最近批准了莱卡奈单抗(lecanemab)和多那奈单抗(donanemab)用于治疗早期症状性阿尔茨海默病(AD)。这两种抗淀粉样蛋白 β 单克隆抗体代表了疾病改变疗法(DMT)治疗阿尔茨海默病的最新希望,这无疑为 DMT 重燃了新的希望,以应对阿尔茨海默病带来的惊人的经济和人力成本。然而,除了这两种成功的抗体外,为了满足AD的治疗需求,人们在开发DMTs的各个方面都做出了巨大的努力。在这篇综述中,我们阐述了各种 DMTs 的核心原理和方法,涵盖了已停止、已完成或正在进行的候选药物临床试验的进展,以及脑刺激和生活方式干预。此外,我们还希望通过对各种候选分子命运的观察,为前瞻性方法和有前景的DTMs治疗AD的应用提供参考和思路,尤其是在普适性和临床应用经济性方面,以便在未来优化疗效,最大限度地造福AD患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Disease-modifying therapies for Alzheimer’s disease: Clinical trial progress and opportunity
The U.S. Food and Drug Administration (FDA) recently approved lecanemab and donanemab for the treatment of early symptomatic Alzheimer's disease (AD) after their phase III trials reached endpoints. These two anti-amyloid β monoclonal antibodies represent the latest promise of disease-modifying therapy (DMT) for AD, which undoubtedly reignites new hope for DMTs to combat the staggering financial and human costs of AD. However, in addition to these two successful antibodies, there have been enormous efforts to develop DMTs in various aspects to meet the therapeutic requirement of AD. In this review, we delineate the core principles and methodologies of diverse DMTs, covering the advances in clinical trials of drug candidates that either have been discontinued, completed, or are ongoing, as well as brain stimulation and lifestyle interventions. In addition, by overseeing the fate of various candidate molecules, we hope to provide references and ideas for prospective approaches and promising applications of DTMs for AD, particularly in terms of universality and clinical application economics, to optimize efficacy and maximize AD patient benefits in the future.
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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
期刊介绍: With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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