Jayaprakash Nandhini, Elumalai Karthikeyan
Department of Pharmaceutics, Saveetha Institute of Medical and Technical Sciences, Saveetha College of Pharmacy Saveetha University Chennai India.
Department of Pharmaceutical Chemistry, Saveetha Institute of Medical and Technical Sciences, Saveetha College of Pharmacy Saveetha University Chennai India.
Chronic Dis Transl Med. 2024 Dec 16;11(2):105-116. doi: 10.1002/cdt3.155. eCollection 2025 Jun.
Substantial research has been conducted to identify an efficient treatment for Alzheimer's disease (AD). Existing treatments, including cholinesterase inhibitors and N-methyl D-aspartate (NMDA) receptor antagonists, do not reverse or slow the disease course but only treat its manifestations. This limitation has brought attention to the need for treatments that modify the amyloid-beta (Aβ) and tau pathology of the disease. One recent advancement in AD treatment is donanemab, a monoclonal antibody intended to clear Aβ plaques in the brain. It targets pyroglutamyl(3)-Aβ protein (3-42) to remove Aβ deposits and alter the disease course. This review explores the timeline of donanemab use from discovery to clinical use. The pharmacodynamics and pharmacokinetics of the drug are discussed along with typical and suboptimal preclinical and clinical trial results in terms of efficacy, safety, and tolerability. Thus, donanemab is more effective than donepezil and rivastigmine in removing plaques and improving cognition. At the same time, it is not devoid of safety concerns that are typical of the majority of amyloid-targeted medicines. The control to end the treatment after plaque cleaning is a unique selling point for some patients, making it more attractive. The innovation and development of donanemab from research to clinical practice are a clear representation of the role of the field of translational medicine in the practical application of new knowledge in the treatment of AD.
为了确定治疗阿尔茨海默病（AD）的有效方法，人们已经进行了大量研究。现有的治疗方法，包括胆碱酯酶抑制剂和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，不能逆转或减缓疾病进程，只能治疗其症状。这一局限性使得人们开始关注能够改变该疾病淀粉样蛋白-β（Aβ）和tau病理的治疗方法。AD治疗领域最近的一项进展是多奈单抗，一种旨在清除大脑中Aβ斑块的单克隆抗体。它靶向焦谷氨酰（3）-Aβ蛋白（3-42）以清除Aβ沉积物并改变疾病进程。本综述探讨了多奈单抗从发现到临床应用的时间线。文中讨论了该药物的药效学和药代动力学，以及在疗效、安全性和耐受性方面典型的和次优的临床前及临床试验结果。因此，多奈单抗在清除斑块和改善认知方面比多奈哌齐和卡巴拉汀更有效。同时，它也并非没有大多数以淀粉样蛋白为靶点的药物所共有的安全问题。对于一些患者来说，在斑块清除后控制并结束治疗是一个独特的卖点，使其更具吸引力。多奈单抗从研究到临床实践的创新与发展清楚地体现了转化医学领域在AD治疗新知识实际应用中的作用。
