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阿杜卡奴单抗在阿尔茨海默病中的卷土重来:陈酒换新瓶。

"Aducanumab" making a comeback in Alzheimer's disease: An old wine in a new bottle.

机构信息

Chitkara College of Pharmacy, Chitkara University, Punjab, India.

Chitkara College of Pharmacy, Chitkara University, Punjab, India.

出版信息

Biomed Pharmacother. 2022 Apr;148:112746. doi: 10.1016/j.biopha.2022.112746. Epub 2022 Feb 26.

Abstract

Despite presence of substantial evidence suggesting the pivotal role of amyloid (Aβ) in Alzheimer's disease (AD), very few therapeutic agents have been able to ameliorate the disease. This paved the way for the discovery of antibody-based immunotherapy to ace Aβ clearance and curb neuronal toxicity, resulting in revival of aducanumab, which following its entry into the brain, interacts with the parenchymal amyloid and decreases Aβ concentration, in a dose-dependent manner. However, the surprising approval from the FDA has created a controversy among healthcare professionals, due to Alzheimer's related imaging abnormality (ARIA) and hypersensitivity, serving as backlogs in its acceptance. Therefore, aducanumab is recognised as being "risen from the grave", accompanied with contrasting statements within the healthcare paradigm. The manuscript provides a collection of data, aiming to elucidate, both the commendable and critical faces, simultaneously intending to gain the attention of the global researchers towards the possibility of disease-modifying therapy in AD. The manuscript discusses the failure of anti-amyloid therapies in AD, that have accelerated the need to find a suitable therapeutic approach, followed by the discussion of timeline and impact of aducanumab in AD models, alongside the controversial judgement raising significant question. Besides, the authors throw some light on the onco-therapeutic implications of the drug approval, which is identified as a significant consequence of the event. The text provides a holistic picture of the drug action, and enlists the considerations for the future, that might be beneficial to both the acceptance of the drug, and the treatment of the disease.

摘要

尽管有大量证据表明淀粉样蛋白 (Aβ) 在阿尔茨海默病 (AD) 中的关键作用,但很少有治疗药物能够改善这种疾病。这为发现基于抗体的免疫疗法铺平了道路,以清除 Aβ 并抑制神经元毒性,从而使 aducanumab 得以复兴,这种药物进入大脑后,与实质淀粉样蛋白相互作用,以剂量依赖的方式降低 Aβ 浓度。然而,由于与阿尔茨海默病相关的成像异常 (ARIA) 和过敏反应,FDA 的令人惊讶的批准在医疗保健专业人员中引起了争议,这成为其接受的障碍。因此,aducanumab 被认为是“起死回生”,在医疗保健模式中存在相互矛盾的观点。本文提供了一系列数据,旨在阐明值得称赞和批评的方面,同时旨在引起全球研究人员对 AD 疾病修饰治疗的可能性的关注。本文讨论了 AD 中的抗淀粉样蛋白治疗失败,这加速了寻找合适治疗方法的必要性,随后讨论了 aducanumab 在 AD 模型中的时间线和影响,以及引发重大问题的有争议的判断。此外,作者还探讨了药物批准的肿瘤治疗意义,这被认为是该事件的一个重要后果。本文提供了药物作用的全貌,并列出了未来的考虑因素,这可能对药物的接受和疾病的治疗都有益。

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