aNeurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari bDepartment of Clinical Research in Neurology, University of Bari Aldo Moro, 'Pia Fondazione Cardinale G. Panico', Tricase, Lecce cResearch and Development Department, Chiesi Farmaceutici, Parma dGeriatric Medicine-Memory Unit and Rare Disease Centre, University of Bari Aldo Moro, Bari, Italy.
Curr Opin Psychiatry. 2014 Mar;27(2):128-37. doi: 10.1097/YCO.0000000000000041.
We reviewed clinical trials on active and passive anti-β-amyloid (Aβ) immunotherapy for the treatment of Alzheimer's disease with a particular focus on monoclonal antibodies against Aβ.
Studies on anti-Alzheimer's disease immunotherapy published in the period from January 2012 to October 2013 were reviewed.
Both active and passive anti-Aβ immunotherapies were shown to clear brain Aβ deposits. However, an active anti-Aβ vaccine (AN1792) has been discontinued because it caused meningoencephalitis in 6% of Alzheimer's disease patients treated. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of Aβ, were disappointing. Another antibody, solanezumab, directed at the mid-region of Aβ, failed in two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients. A third Phase III study with solanezumab is ongoing in mildly affected Alzheimer's disease patients based on encouraging results in this subgroup of patients. Second-generation active Aβ vaccines (ACC-001, CAD106, and Affitope AD02) and new passive anti-Aβ immunotherapies (gantenerumab and crenezumab) are being tested in prodromal Alzheimer's disease patients, in presymptomatic individuals with Alzheimer's disease-related mutations, or in asymptomatic individuals at risk of developing Alzheimer's disease to definitely test the Aβ cascade hypothesis of Alzheimer's disease.
我们回顾了针对阿尔茨海默病的主动和被动抗β-淀粉样蛋白（Aβ）免疫疗法的临床试验，重点关注针对 Aβ 的单克隆抗体。
综述了 2012 年 1 月至 2013 年 10 月期间发表的关于抗阿尔茨海默病免疫疗法的研究。
主动和被动抗 Aβ 免疫疗法均能清除脑内 Aβ 沉积。然而，一种主动 Aβ 疫苗（AN1792）因在 6%接受治疗的阿尔茨海默病患者中引发脑膜炎而被停用。在被动免疫疗法中，两种针对轻度至中度阿尔茨海默病患者的 bapineuzumab（一种针对 Aβ N 端序列的人源化单克隆抗体）的 III 期临床试验令人失望。另一种针对 Aβ 中部的抗体 solanezumab 在两项针对轻度至中度阿尔茨海默病患者的 III 期临床试验中失败。另一个基于对轻度影响的阿尔茨海默病患者的亚组中令人鼓舞的结果的 III 期研究正在进行中。第二代主动 Aβ 疫苗（ACC-001、CAD106 和 Affitope AD02）和新的被动抗 Aβ 免疫疗法（gantenerumab 和 crenezumab）正在进行临床试验，用于前驱期阿尔茨海默病患者、有阿尔茨海默病相关突变的无症状个体或有发展为阿尔茨海默病风险的无症状个体，以明确测试阿尔茨海默病的 Aβ 级联假说。
