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Active Immunotherapy to Prevent Alzheimer Disease-A DNA Amyloid β 1-42 Trimer Vaccine.
JAMA Neurology ( IF 29.0 ) Pub Date : 2020-03-01 , DOI: 10.1001/jamaneurol.2019.4182
Roger N Rosenberg 1 , Doris Lambracht-Washington 1
Affiliation  

Immunotherapy directed to reduce amyloid levels in the brains of patients with Alzheimer disease (AD) and provide clinical benefit has not definitely been successful using either passive immunizations with preformed antiamyloid (anti-Aβ42 as the toxic processed form of amyloid β protein), monoclonal antibodies (moabs), or active immunization with amyloid peptides. A recent press release by Biogen1 has indicated that their moab aducanumab has shown clinical benefit after reanalysis of larger data panels of a phase 3 clinical trial that ended in March 2019. This reanalysis has not been published or reproduced, but it is potentially an important finding and supportive of immunotherapy for AD. Thus, antiamyloid immunotherapy still holds promise for clinical benefit, as amyloid (Aβ) accumulation in the brain can be detected decades before the onset of symptoms and amyloid accumulation is a trigger for many downstream pathologies, such as loss of neuronal plasticity, tau hyperphosphorylation, and frank neuronal death. Targeting more than one pathology with a single therapy, as we have shown for the DNA Aβ42 trimer vaccine, might be the path forward in finding an option for AD prevention or delay of disease progression.2



中文翻译:

预防阿尔茨海默病的主动免疫疗法-A DNA 淀粉样蛋白 β 1-42 三聚体疫苗。

旨在降低阿尔茨海默病 (AD) 患者大脑中的淀粉样蛋白水平并提供临床益处的免疫疗法使用预先形成的抗淀粉样蛋白(抗 Aβ42 作为淀粉样蛋白 β 蛋白的毒性加工形式)的被动免疫、单克隆抗体并没有绝对成功(moabs),或用淀粉样肽主动免疫。Biogen 1最近的新闻稿已经表明,他们的 moab aducanumab 在对 2019 年 3 月结束的 3 期临床试验的更大数据组进行重新分析后显示出临床益处。该重新分析尚未发表或复制,但它可能是 AD 免疫疗法的重要发现和支持. 因此,抗淀粉样蛋白免疫疗法仍然有望带来临床益处,因为可以在症状出现前几十年检测到大脑中的淀粉样蛋白 (Aβ) 积累,并且淀粉样蛋白积累是许多下游病理的触发因素,例如神经元可塑性丧失、tau 过度磷酸化、和坦率的神经元死亡。正如我们在 DNA Aβ42 三聚体疫苗中所展示的那样,通过单一疗法靶向不止一种病理学,可能是寻找预防 AD 或延缓疾病进展的选择的前进道路。2

更新日期:2020-03-09
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