Department of Basic Medicine, Neuroscience, and Sense Organs, Neurodegenerative Disease Unit, University of Bari Aldo Moro, Bari, Italy.
Expert Rev Clin Immunol. 2014 Mar;10(3):405-19. doi: 10.1586/1744666X.2014.883921. Epub 2014 Feb 4.
Both active and passive anti-β-amyloid (Aβ) immunotherapies for the treatment of Alzheimer's disease (AD) have demonstrated clearance of brain Aβ deposits. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate AD patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of Aβ, were disappointing. Also solanezumab, directed at the mid-region of Aβ, failed in two Phase III trials in mild-to-moderate AD. Another Phase III trial with solanezumab is ongoing in mildly affected AD patients based on encouraging results in this subgroup. Second-generation active Aβ vaccines (CAD106, ACC-001, and Affitope AD02) and new passive anti-Aβ immunotherapies (gantenerumab and crenezumab) have been developed and are under clinical testing. These new anti-Aβ immunotherapies are being tested in prodromal AD, in presymptomatic subjects with AD-related mutations, or in asymptomatic subjects at risk of developing AD. These primary and secondary prevention trials will definitely test the Aβ cascade hypothesis of AD.
针对阿尔茨海默病（AD）的主动和被动抗β-淀粉样蛋白（Aβ）免疫疗法都已证明可清除脑内 Aβ 沉积。在被动免疫疗法中，两种针对 Aβ 氨基端序列的人源化单克隆抗体 bapineuzumab 在轻中度 AD 患者的两项 III 期临床试验令人失望。另一种针对 Aβ 中段的 solanezumab 在两项轻中度 AD 的 III 期临床试验中也失败了。基于该亚组的令人鼓舞的结果，另一个针对轻度 AD 患者的 solanezumab III 期试验正在进行中。第二代主动 Aβ 疫苗（CAD106、ACC-001 和 Affitope AD02）和新型被动抗 Aβ 免疫疗法（gantenerumab 和 crenezumab）已被开发并正在进行临床测试。这些新型抗 Aβ 免疫疗法正在进行前驱 AD、AD 相关突变的无症状前体或有 AD 发病风险的无症状受试者的临床试验。这些一级和二级预防试验将肯定会检验 AD 的 Aβ级联假说。
