Panza Francesco, Seripa Davide, Lozupone Madia, Solfrizzi Vincenzo, Imbimbo Bruno P, Barulli Maria Rosaria, Tortelli Rosanna, Capozzo Rosa, Bisceglia Paola, Dimitri Andrea, Stallone Roberta, Dibello Vittorio, Quaranta Nicola, Daniele Antonio, Bellomo Antonello, Greco Antonio, Logroscino Giancarlo
a Unit of Neurodegenerative Disease, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro' , Bari , Italy.
b Unit of Neurodegenerative Disease, Department of Clinical Research in Neurology , University of Bari 'Aldo Moro' at 'Pia Fondazione Card. G. Panico' , Tricase , Italy.
Expert Opin Biol Ther. 2018 Jan;18(1):25-35. doi: 10.1080/14712598.2018.1389885. Epub 2017 Oct 16.
The recent failure of several clinical trials on anti-β-amyloid (Aβ) drugs in Alzheimer's disease (AD) suggested earlier intervention in the disease course. Secondary prevention trials have been started in autosomal-dominant AD (ADAD) individuals without cognitive dysfunction and in cognitively healthy subjects at risk of developing sporadic AD (SAD).
Herein, the authors discuss prevention trials in ADAD and SAD, with a focus on the anti-Aβ monoclonal antibodies solanezumab and gantenerumab presently in Phase III clinical development. These therapies are also being tested in the Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU).
Anti-Aβ monoclonal antibodies are being tested in subjects at the preclinical stage of ADAD and even in symptom-free subjects at risk of developing SAD. The subsequent DIAN-TU Adaptive Prevention Trial is a 4-year study that will assess whether such biomarker effects may stop the progress of the AD process, preventing cognitive symptoms. The hope is to interfere in the disease course when it is not too late. A clinical success of these prevention trials would represent the proof of the Aβ hypothesis of AD.
近期多项针对阿尔茨海默病（AD）的抗β淀粉样蛋白（Aβ）药物临床试验失败，这表明需要在疾病进程中更早地进行干预。目前已针对无认知功能障碍的常染色体显性AD（ADAD）个体以及有患散发性AD（SAD）风险的认知健康受试者开展了二级预防试验。
在此，作者讨论了ADAD和SAD的预防试验，重点关注目前正处于III期临床开发阶段的抗Aβ单克隆抗体索拉珠单抗和甘特珠单抗。这些疗法也正在显性遗传性阿尔茨海默病网络试验单元（DIAN-TU）中进行测试。
抗Aβ单克隆抗体正在ADAD临床前期受试者甚至有患SAD风险的无症状受试者中进行测试。随后的DIAN-TU适应性预防试验是一项为期4年的研究，将评估此类生物标志物效应是否可能阻止AD进程的进展，预防认知症状。人们希望在为时未晚之时干预疾病进程。这些预防试验的临床成功将代表AD的Aβ假说得到证实。
