Beshir Semira Abdi, Hussain Nadia, Menon Vineetha Bharathan, Al Haddad Amal H I, Al Zeer Rahaf Adnan Kh, Elnour Asim Ahmed
Department of Pharmacy Practice Dubai Pharmacy College for Girls, Dubai, UAE.
Department of Pharmaceutical Sciences College of Pharmacy Al Ain University, Al Ain, UAE.
Int J Alzheimers Dis. 2024 Jul 23;2024:2052142. doi: 10.1155/2024/2052142. eCollection 2024.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder caused by the accumulation of amyloid-beta (A) proteins and neurofibrillary tangles in the brain. There have been recent advancements in antiamyloid therapy for AD. This narrative review explores the recent advancements and challenges in antiamyloid therapy. In addition, a summary of evidence from antiamyloid therapy trials is presented with a focus on lecanemab. Lecanemab is the most recently approved monoclonal antibody that targets A protofibrils for the treatment of patients with early AD and mild cognitive impairment (MCI). Lecanemab was the first drug shown to slow cognitive decline in patients with MCI or early onset AD dementia when administered as an infusion once every two weeks. In the Clarity AD trial, lecanemab was associated with infusion-site reactions (26.4%) and amyloid-related imaging abnormalities (12.6%). The clinical relevance and long-term side effects of lecanemab require further longitudinal observation. However, several challenges must be addressed before the drug can be routinely used in clinical practice. The drug's route of administration, need for imaging and genetic testing, affordability, accessibility, infrastructure, and potential for serious side effects are some of these challenges. Lecanemab's approval has fueled interest in the potential of other antiamyloid therapies, such as donanemab. Future research must focus on developing strategies to prevent AD; identify easy-to-use validated plasma-based assays; and discover newer user-friendly, and cost-effective drugs that target multiple pathways in AD pathology.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，由大脑中β-淀粉样蛋白（A）的积累和神经原纤维缠结引起。近期AD的抗淀粉样蛋白治疗取得了进展。本叙述性综述探讨了抗淀粉样蛋白治疗的最新进展和挑战。此外，还介绍了抗淀粉样蛋白治疗试验的证据总结，重点是lecanemab。Lecanemab是最近获批的单克隆抗体，靶向A原纤维，用于治疗早期AD和轻度认知障碍（MCI）患者。Lecanemab是第一种被证明在每两周静脉输注一次时能减缓MCI或早发性AD痴呆患者认知衰退的药物。在Clarity AD试验中，lecanemab与输注部位反应（26.4%）和淀粉样蛋白相关成像异常（12.6%）有关。Lecanemab的临床相关性和长期副作用需要进一步的纵向观察。然而，在该药物能够在临床实践中常规使用之前，必须解决几个挑战。这些挑战包括药物的给药途径、成像和基因检测的需求、可负担性、可及性、基础设施以及严重副作用的可能性。Lecanemab的获批激发了人们对其他抗淀粉样蛋白疗法（如donanemab）潜力的兴趣。未来的研究必须专注于制定预防AD的策略；确定易于使用的经过验证的基于血浆的检测方法；并发现更新的、用户友好且具有成本效益的药物，这些药物可靶向AD病理学中的多种途径。
