阿尔茨海默病的药物研发：我们现在何处，又将走向何方？
Drug development for Alzheimer's disease: where are we now and where are we headed?
作者信息
Sabbagh Marwan N
机构信息
The Cleo Roberts Center for Clinical Research, Banner-Sun Health Research Institute, Sun City, AZ 85351, USA.
出版信息
Am J Geriatr Pharmacother. 2009 Jun;7(3):167-85. doi: 10.1016/j.amjopharm.2009.06.003.
OBJECTIVE
The aim of this article was to provide a survey of the clinical development of pharmacotherapy for Alzheimer's disease (AD).
METHODS
A search of PubMed to identify pertinent English-language literature was conducted using the terms Alzheimer's disease AND clinical trials (2003-2008), dementia AND prevention AND clinical trials (2003-2008), and the chemical names of all compounds mentioned in articles on new drugs for AD published since 2005. www.ClinicalTrials.gov was searched for relevant trials. Abstracts of the 2008 International Conference on Alzheimer's Disease (ICAD) were reviewed for relevance, as were pharmaceutical company and AD advocacy Web sites. Articles selected for review were primary reports of data from preclinical studies and clinical trials.
RESULTS
A large number of drugs with differing targets and mechanisms of action are under development for the treatment of AD. Phase III trials of Ginkgo biloba, NSAIDs, phenserine, statins, tarenflurbil, tramiprosate, and xaliproden have been completed, none of them demonstrating adequate efficacy. Encouraging results from completed Phase II trials of dimebon, huperzine A, intravenous immunoglobulin, and methylthioninium chloride were reported at ICAD 2008. Nineteen compounds are currently in Phase II trials, and 3 compounds (AN1792, lecozotan SR, and SGS742) failed at this stage of development.
CONCLUSIONS
Despite disappointing results from recently completed Phase III trials of several novel compounds, the extent and breadth of activity at all phases of clinical development suggest that new pharmacotherapeutic options for the treatment of AD will become available within the next decade.
目的
本文旨在对阿尔茨海默病（AD）药物治疗的临床进展进行综述。
方法
使用“阿尔茨海默病”和“临床试验（2003 - 2008）”、“痴呆”和“预防”以及“临床试验（2003 - 2008）”等检索词在PubMed上搜索相关英文文献，并检索了自2005年以来发表的关于AD新药文章中提及的所有化合物的化学名称。在www.ClinicalTrials.gov上搜索相关试验。对2008年国际阿尔茨海默病会议（ICAD）的摘要以及制药公司和AD宣传网站进行相关性审查。入选综述的文章为临床前研究和临床试验数据的初步报告。
结果
目前有大量针对不同靶点和作用机制的药物正在研发用于治疗AD。银杏叶提取物、非甾体抗炎药、苯西酯、他汀类药物、塔伦氟比、曲美司他和卡立普多的III期试验已经完成，但均未显示出足够的疗效。在2008年ICAD会议上报告了已完成的II期试验中，二甲金刚胺、石杉碱甲、静脉注射免疫球蛋白和亚甲蓝取得了令人鼓舞的结果。目前有19种化合物处于II期试验阶段，3种化合物（AN1792、长效左旋唑坦和SGS742）在该开发阶段失败。
结论
尽管最近几种新型化合物的III期试验结果令人失望，但临床开发各阶段的研究范围和广度表明，未来十年内将有新的药物治疗方案可用于治疗AD。
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