Beta-amyloidbased immunotherapy as a treatment of Alzheimers disease.
The pathology of Alzheimer's disease shows a significant correlation between beta-amyloid peptide conformation and the clinical severity of dementia. For many years efforts have been focused on the development of inhibitors of beta-amyloid formation and its related neurotoxic effects. A new concept has been developed which shows that site-directed antibodies may modulate formation of beta-amyloid. The performance of anti-beta-amyloid antibodies in transgenic mice models of Alzheimer's disease showed that they are delivered to the central nervous system, preventing in vivo formation of beta-amyloid. Moreover, those antibodies dissolve beta-amyloid plaques and protect the mice from learning and age-related memory deficits. Experimental active immunization with beta-amyloid (1-42) in humans was stopped in phase II of their clinical trials. However, several new preparations, able to provide antibodies against beta-amyloid by either active or passive routes, have been formulated and have reached clinical testing. The data presented support the hypothesis that beta-amyloid peptide plays a central role in Alzheimer's disease, and antibodies which modulate beta-amyloid conformation may lead to immunotherapy of the disease.
Solomon
Beka
B
Department of Molecular Microbiology & Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel. beka@post.tau.ac.il
D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007167:Immunotherapy
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D016756:Immunoglobulins, Intravenous