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被动抗淀粉样β单克隆抗体:过去20年的经验教训

Passive Anti-amyloid Beta Monoclonal Antibodies: Lessons Learned over Past 20 Years.

作者信息

Wicker Alexandra, Shriram Jahnavi, Decourt Boris, Sabbagh Marwan Noel

机构信息

Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, USA.

Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.

出版信息

Neurol Ther. 2024 Dec;13(6):1571-1595. doi: 10.1007/s40120-024-00664-z. Epub 2024 Oct 8.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that significantly impairs cognitive and functional abilities, placing a substantial burden on both patients and caregivers. Current symptomatic treatments fail to halt the progression of AD, highlighting the urgent need for more effective disease-modifying therapies (DMTs). DMTs under development are classified as either passive or active on the basis of their mechanisms of eliciting an immune response. While this review will touch on active immunotherapies, we primarily focus on anti-amyloid beta monoclonal antibodies (mAbs), a form of passive immunotherapy, discussing their multifaceted role in AD treatment and the critical factors influencing their therapeutic efficacy. With two mAbs now approved and prescribed in the clinical setting, it is crucial to reflect on the lessons learned from trials of earlier mAbs that have shaped their development and contributed to their current success. These insights can then guide the creation of even more effective mAbs, ultimately enhancing therapeutic outcomes for patients with AD while minimizing adverse events.

摘要

阿尔茨海默病(AD)是一种神经退行性疾病,会严重损害认知和功能能力,给患者和护理人员带来沉重负担。目前的对症治疗无法阻止AD的进展,这凸显了对更有效的疾病修饰疗法(DMTs)的迫切需求。根据引发免疫反应的机制,正在研发的DMTs分为被动型或主动型。虽然本综述将涉及主动免疫疗法,但我们主要关注抗淀粉样β单克隆抗体(mAbs),这是一种被动免疫疗法形式,讨论它们在AD治疗中的多方面作用以及影响其治疗效果的关键因素。随着两种mAbs现已在临床环境中获批并开出处方,反思从早期mAbs试验中吸取的经验教训至关重要,这些经验教训塑造了它们的发展并促成了它们目前的成功。这些见解随后可以指导研发更有效的mAbs,最终提高AD患者的治疗效果,同时将不良事件降至最低。

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