P.S. Aisen, University of Southern California Alzheimer's Therapeutic Research Institute, San Diego, CA, USA,
J Prev Alzheimers Dis. 2020;7(3):146-151. doi: 10.14283/jpad.2020.24.
The termination of many clinical trials of amyloid-targeting therapies for the treatment of Alzheimer's disease (AD) has had a major impact on the AD clinical research enterprise. However, positive signals in recent studies have reinvigorated support for the amyloid hypothesis and amyloid-targeting strategies. In December 2019, the EU-US Clinical Trials on Alzheimer's Disease (CTAD) Task Force met to share learnings from these studies in order to inform future trials and promote the development of effective AD treatments. Critical factors that have emerged in studies of anti-amyloid monoclonal antibody therapies include developing a better understanding of the specific amyloid species targeted by different antibodies, advancing our insight into the mechanism by which those antibodies may reduce pathology, implementing more comprehensive repertoires of biomarkers into trials, and identifying appropriate doses. Studies suggest that Amyloid-Related Imaging Abnormalities - effusion type (ARIA-E) are a manageable safety concern and that caution should be exercised before terminating studies based on interim analyses. The Task Force concluded that opportunities for developing effective treatments include developing new biomarkers, intervening in early stages of disease, and use of combination therapies.
许多针对阿尔茨海默病（AD）的淀粉样蛋白靶向治疗的临床试验已经终止，这对 AD 的临床研究产生了重大影响。然而，最近的研究中出现的积极信号，重新激发了人们对淀粉样蛋白假说和淀粉样蛋白靶向策略的支持。2019 年 12 月，欧盟-美国针对 AD 的临床试验（CTAD）工作组举行会议，分享这些研究中的经验教训，以为未来的试验提供信息，并促进有效的 AD 治疗方法的发展。在抗淀粉样蛋白单克隆抗体治疗研究中出现的关键因素包括：更好地了解不同抗体针对的特定淀粉样蛋白种类；深入了解这些抗体可能减少病理学的机制；在试验中纳入更全面的生物标志物谱；以及确定合适的剂量。研究表明，淀粉样蛋白相关成像异常-渗出型（ARIA-E）是一种可管理的安全问题，在基于中期分析终止研究之前应谨慎行事。工作组得出结论，开发有效治疗方法的机会包括开发新的生物标志物、干预疾病的早期阶段以及使用联合疗法。
