Naoyuki Suzuki, Takuya Hatta, Mana Ito, Ken-Ichi Kusakabe
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引用次数: 0
Abstract
Amyloid-β (Aβ) plaques and neurofibrillary tangles containing phosphorylated tau protein are major hallmarks of Alzheimer's disease (AD). Drug discovery efforts to target Aβ and tau have been the primary focus for several decades. Recently, substantial breakthroughs have been achieved in the clinical development of Aβ antibodies; aducanumab was approved under conditional accelerated pathway by Food and Drug Administration (FDA) in the U.S. as the first disease-modifying agent for treating AD, and lecanemab has been granted traditional full approved in the U.S. and Japan. In addition, donanemab met the primary endpoint in a phase 3 study. On the other hand, tau-targeting therapies have failed to show clinical benefit although that increased tau levels show a strong correlation with cognitive impairment relative to Aβ depositions. Currently, tau immunotherapies, such as anti-tau antibodies and tau vaccines, have shown functional benefits in clinical trials. Also, clinical trials for combination therapy of Aβ and tau antibodies to see their potential are being investigated. In this review, we provide updates on the results of clinical trials of anti-Aβ antibodies and anti-tau therapeutics and suggest future directions for these therapeutics.
淀粉样β(Aβ)斑块和含有磷酸化tau蛋白的神经纤维缠结是阿尔茨海默病(AD)的主要特征。几十年来,针对 Aβ 和 tau 的药物研发工作一直是主要焦点。最近,Aβ 抗体的临床开发取得了重大突破:美国食品药品管理局(FDA)有条件加速批准了 aducanumab 作为首个治疗 AD 的疾病改变药物,而 lecanemab 则在美国和日本获得了传统的全面批准。此外,多奈单抗在一项三期研究中达到了主要终点。另一方面,尽管相对于Aβ沉积物,tau水平的升高与认知障碍有很强的相关性,但tau靶向疗法未能显示出临床益处。目前,抗 tau 抗体和 tau 疫苗等 tau 免疫疗法已在临床试验中显示出功能性益处。此外,Aβ和tau抗体联合疗法的临床试验也在进行中,以了解其潜力。在这篇综述中,我们将介绍抗Aβ抗体和抗tau疗法临床试验的最新结果,并提出这些疗法的未来发展方向。
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