Geriatric Unit and Gerontology-Geriatric Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Curr Alzheimer Res. 2011 Dec;8(8):808-17. doi: 10.2174/156720511798192718.
Recent advances in our understanding of the neurobiology of Alzheimer's disease (AD) have led to the development of putative disease-modifying treatments. The most revolutionary of these approaches consists in the removal of brain β-amyloid (Aβ) via anti-Aβ antibodies. Brain imaging and neuropathological studies have shown the ability of both active and passive anti-Aβ immunotherapies of clearing Aβ deposits from the brain of the AD patients. An active anti-Aβ vaccine preparation, AN1792, has been used in AD patients with some clues of clinical efficacy but causing meningoencephalitis in about 6% of patients and it has been abandoned. Several second-generation active Aβ vaccines and passive Aβ immunotherapies have been developed and are under clinical investigation with the aim of accelerating Aβ clearance from the brain of the AD patients. The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Aβ monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce Aβ burden in the brain of AD patients. However, the preliminary cognitive efficacy of bapineuzumab appears uncertain. The occurrence of vasogenic edema, especially in apolipoprotein E 4 carriers, may limit its clinical use and have led to abandon the highest dose of the drug (2 mg/kg). The results of four ongoing large Phase III trials on bapineuzumab will tell us if passive anti-Aβ immunization is able to alter the course if this devastating disease.
我们对阿尔茨海默病（AD）神经生物学的理解的最新进展导致了潜在的疾病修饰治疗方法的发展。这些方法中最具革命性的方法是通过抗β-淀粉样蛋白（Aβ）抗体去除大脑中的β-淀粉样蛋白（Aβ）。脑成像和神经病理学研究表明，主动和被动抗 Aβ 免疫疗法均具有清除 AD 患者大脑中 Aβ 沉积的能力。一种主动的抗 Aβ 疫苗制剂 AN1792 已在 AD 患者中使用，具有一些临床疗效的线索，但约 6%的患者会导致脑膜炎脑炎，现已被放弃。已经开发了几种第二代主动 Aβ 疫苗和被动 Aβ 免疫疗法，并正在进行临床试验，目的是加速 AD 患者大脑中 Aβ 的清除。这些免疫方法中最先进的是 bapineuzumab，由人源化抗 Aβ 单克隆抗体组成，已在两项 II 期临床试验中进行了测试，证明可以减轻 AD 患者大脑中的 Aβ 负担。然而，bapineuzumab 的初步认知疗效似乎不确定。血管源性水肿的发生，特别是在载脂蛋白 E4 携带者中，可能会限制其临床应用，并导致放弃该药物的最高剂量（2mg/kg）。四项正在进行的 bapineuzumab 大型 III 期试验的结果将告诉我们，被动抗 Aβ 免疫是否能够改变这种毁灭性疾病的病程。
