Schreiner Thomas Gabriel, Croitoru Cristina Georgiana, Hodorog Diana Nicoleta, Cuciureanu Dan Iulian
Department of Medical Specialties III, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania.
First Neurology Clinic, "N. Oblu" Clinical Emergency Hospital, 700309 Iasi, Romania.
Biomedicines. 2024 May 15;12(5):1096. doi: 10.3390/biomedicines12051096.
Alzheimer's disease, the most common type of dementia worldwide, lacks effective disease-modifying therapies despite significant research efforts. Passive anti-amyloid immunotherapies represent a promising avenue for Alzheimer's disease treatment by targeting the amyloid-beta peptide, a key pathological hallmark of the disease. This approach utilizes monoclonal antibodies designed to specifically bind amyloid beta, facilitating its clearance from the brain. This review offers an original and critical analysis of anti-amyloid immunotherapies by exploring several aspects. Firstly, the mechanisms of action of these therapies are reviewed, focusing on their ability to promote Aβ degradation and enhance its efflux from the central nervous system. Subsequently, the extensive history of clinical trials involving anti-amyloid antibodies is presented, from initial efforts using first-generation molecules leading to mixed results to recent clinically approved drugs. Along with undeniable progress, the authors also highlight the pitfalls of this approach to offer a balanced perspective on this topic. Finally, based on its potential and limitations, the future directions of this promising therapeutic strategy for Alzheimer's disease are emphasized.
阿尔茨海默病是全球最常见的痴呆类型,尽管进行了大量研究,但仍缺乏有效的疾病修正疗法。被动抗淀粉样蛋白免疫疗法通过靶向淀粉样β肽(该疾病的关键病理标志),为阿尔茨海默病的治疗提供了一条有前景的途径。这种方法利用设计用于特异性结合淀粉样β的单克隆抗体,促进其从大脑中清除。本综述通过探讨几个方面,对抗淀粉样蛋白免疫疗法进行了原创性的批判性分析。首先,回顾了这些疗法的作用机制,重点关注它们促进Aβ降解和增强其从中枢神经系统流出的能力。随后,介绍了涉及抗淀粉样蛋白抗体的临床试验的广泛历史,从使用第一代分子的初步努力导致的混合结果到最近临床批准的药物。在取得不可否认的进展的同时,作者还强调了这种方法的缺陷,以便对该主题提供一个平衡的观点。最后,基于其潜力和局限性,强调了这种有前景的阿尔茨海默病治疗策略的未来方向。