治疗阿尔茨海默病创新药物研发进展

Advances in development of innovative drugs for Alzheimer disease

阿尔茨海默病(AD)是一种中枢神经系统退行性疾病,临床表现为进行性认知功能下降和行为损害,因其发病机制复杂,目前尚无有效的预防和治疗手段。近年来,依据AD发病机制和病理学特点进行靶向治疗逐渐成为新药开发的重点。靶向药物β淀粉样蛋白(Aβ)单克隆抗体阿度奴单抗和来卡内单抗获美国FDA批准用于AD的治疗,调节肠道菌群药物甘露特纳在中国批准上市,β分泌酶抑制剂、抗Aβ疫苗、tau蛋白聚集抑制剂等创新药物也表现出对AD的治疗潜力并先后进入临床试验。本文梳理近年来治疗AD的创新药物研究进展,分析创新药物研发策略,为治疗AD和开展相关新药研究提供参考和思路。

Alzheimer disease(AD)is a degenerative disease of the central nervous system,which is characterized by progressive cognitive decline and behavioral impairment,and has no effective prevention and treatment because of its complex pathogenesis.In recent years,targeted therapies based on the pathogenesis and pathology of AD have come to be the focus of new drug development.The targeted drugs amyloid monoclonal antibody aducanumab and lecanemab were approved by the US FDA for the treatment of AD,and GV-971 was approved in China.Innovative drugs such asβ-secretase inhibitors,anti-Aβvaccines,tau protein aggregation inhibitors,andγ-secretase inhibitors have also shown therapeutic potential for AD and entered clinical trials.This paper is intended to sum⁃merize the recent research progress in innovative drugs for the treatment of AD and analyze the strate⁃gies of innovative drug development in order to provide reference and ideas for the treatment of AD and the development of related new drugs.