Anti-beta-Amyloid Immunotherapy for Alzheimer's Disease: Focus on Bapineuzumab

作者：Panza Francesco^*; Frisardi Vincenza; Imbimbo Bruno P; Seripa Davide; Paris Francesco; Santamato Andrea; D'Onofrio Grazia; Logroscino Giancarlo; Pilotto Alberto; Solfrizzi Vincenzo

来源：Current Alzheimer Research, 2011, 8(8): 808-817.

• beta-amyloid
• Alzheimer's disease
• active immunotherapy
• passive immunotherapy
• bapineuzumab

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 beta-amyloid (A beta) via anti-A beta antibodies. Brain imaging and neuropathological studies have shown the ability of both active and passive anti-A beta immunotherapies of clearing A beta deposits from the brain of the AD patients. An active anti-A beta 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 A beta vaccines and passive A beta immunotherapies have been developed and are under clinical investigation with the aim of accelerating A beta clearance from the brain of the AD patients. The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-A beta monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce A beta 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 epsilon 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-A beta immunization is able to alter the course if this devastating disease.

• 出版日期2011-12