Cleveland Clinic Lou Ruvo Center for Brain Health, 9500 Euclid Avenue/U10, Cleveland, OH 44195.
Curr Top Med Chem. 2013;13(18):2306-27. doi: 10.2174/15680266113136660162.
Alzheimer's disease (AD) is the most common cause of dementia and a major cause of morbidity and mortality. The greatest risk factor for AD is age and as many countries are experiencing an aging population, the expected rise in AD threatens to have serious medical and socioeconomic impact in the coming decades. The only approved medications for AD are symptomatic and there are no currently available disease modifying treatments. Hence, a disease modifying treatment is desperately needed for AD not only for proper care and management of affected patients, but also to reduce society's socioeconomic burden. Developing novel compounds for any indication is a time, effort, and money consuming endeavor and most treatments never make it to market. Other research and development strategies are needed, especially for the treatment of AD. We provide a review of the current literature in assessing possibilities of repurposing medications currently used for non-AD indications. Many different compounds from many different pharmacological classes have already been studied in an AD context. We provide a "pragmatic drug repurposing score" for each of these compounds based on type of studies conducted, number of possible mechanisms of action, efficacy in AD and other neurodegenerative disease studies, tolerability profile, and their ability to cross the blood brain barrier. The current data suggest several compounds worthy of further study as treatments for AD. Compounds with the highest scores include lithium, minocycline, exenatide, valproic acid, methylene blue, and nicotine.
阿尔茨海默病（AD）是痴呆症最常见的病因，也是发病率和死亡率的主要原因。AD 的最大风险因素是年龄，随着许多国家的人口老龄化，预计 AD 的发病率上升将在未来几十年对医疗和社会经济造成严重影响。目前唯一批准用于 AD 的药物是对症治疗，尚无可用的疾病修正治疗方法。因此，AD 急需一种疾病修正治疗方法，不仅要对受影响的患者进行适当的护理和管理，还要减轻社会的社会经济负担。开发任何适应症的新型化合物都是一项耗时、费力和耗费资金的努力，而且大多数治疗方法都无法推向市场。因此，需要其他研究和开发策略，特别是用于 AD 的治疗方法。我们回顾了当前文献，评估了重新利用目前用于非 AD 适应症的药物的可能性。许多不同的化合物，来自许多不同的药理学类别，已经在 AD 背景下进行了研究。我们根据进行的研究类型、可能的作用机制数量、在 AD 和其他神经退行性疾病研究中的疗效、耐受性概况以及它们穿过血脑屏障的能力，为这些化合物中的每一种提供了“实用药物再利用评分”。目前的数据表明，有几种化合物值得进一步研究作为 AD 的治疗方法。评分最高的化合物包括锂、米诺环素、艾塞那肽、丙戊酸、亚甲蓝和尼古丁。
