Department of Pharmacology, AIIMS Bhopal, Bhopal, Madhya Pradesh, India.
Department of Pharmacology, Kalpana Chawla Government Medical College, Karnal, Haryana, India.
J Basic Clin Physiol Pharmacol. 2023 Dec 6;35(1-2):25-29. doi: 10.1515/jbcpp-2023-0176. eCollection 2024 Jan 1.
The humanised monoclonal antibody donanemab is being developed to treat early onset Alzheimer's disease (AD). This drug targets N-truncated pyroglutamate amyloid-peptide at position 3 (N3pG), a modified form of deposited amyloid-peptide. The symptoms of Alzheimer's disease include gradual memory loss and other cognitive impairments. This disease is characterized by amyloid plaques, which are formed as a result of an accumulation of amyloid-(A-β) peptides. Despite granting donanemab breakthrough therapy designation in June 2021, the FDA rejected donanemab's accelerated approval application in January 2023, due to inadequate safety data. According to the baseline amyloid level, the time to achieve plaque clearance (amyloid plaque level <24.1 centiloids) varied. Patients with higher baseline levels were more likely to achieve amyloid clearance. The safety of the drug was demonstrated by amyloid-related imaging abnormalities (ARIA), which ranged from 26.1 to 30.5 % in the studies. Clinical trial results have shown that donanemab delays cognitive and functional deterioration in patients with mild to moderate AD. However, it is not yet known whether donenameb offers therapeutic benefits that can change and improve the clinical condition of AD patients. To achieve significant clinical benefits in AD patients with cognitive impairment, further studies may be needed to investigate the interaction between A-β plaque reduction and toxic tau levels.
人源化单克隆抗体 donanemab 被开发用于治疗早发性阿尔茨海默病（AD）。这种药物针对的是 N 端截断焦谷氨酸淀粉样肽在位置 3（N3pG），这是一种已沉积淀粉样肽的修饰形式。阿尔茨海默病的症状包括逐渐丧失记忆和其他认知障碍。这种疾病的特征是淀粉样斑块，这是由于淀粉样-β（A-β）肽的积累而形成的。尽管 2021 年 6 月 donanemab 获得突破性治疗指定，但由于安全性数据不足，FDA 于 2023 年 1 月拒绝了 donanemab 的加速批准申请。根据基线淀粉样蛋白水平，达到斑块清除（淀粉样斑块水平<24.1 百分位数）的时间有所不同。基线水平较高的患者更有可能实现淀粉样蛋白清除。药物的安全性通过淀粉样相关成像异常（ARIA）得到证实，在这些研究中，ARIA 的发生率从 26.1%到 30.5%不等。临床试验结果表明，donanemab 可延缓轻度至中度 AD 患者的认知和功能恶化。然而，目前尚不清楚 donenameb 是否提供可以改变和改善 AD 患者临床状况的治疗益处。为了在认知障碍的 AD 患者中获得显著的临床益处，可能需要进一步研究来研究 A-β 斑块减少与毒性 tau 水平之间的相互作用。
