药物广泛关联研究加（MWAS+）：药物再利用概念验证研究。
Medication-Wide Association Study Plus (MWAS+): A Proof of Concept Study on Drug Repurposing.
机构信息
Department of Clinical Research and Leadership, George Washington University, Washington, DC 20037, USA.
Center for Data Science and Outcome Research, Washington DC VA Medical Center, Washington, DC 20422, USA.
出版信息
Med Sci (Basel). 2022 Aug 31;10(3):48. doi: 10.3390/medsci10030048.
The high cost and time for developing a new drug or repositioning a partially-developed drug has fueled interest in "repurposing" drugs. Drug repurposing is particularly of interest for Alzheimer's disease (AD) or AD-related dementias (ADRD) because there are no unrestricted disease-modifying treatments for ADRD. We have designed and pilot tested a 3-Step Medication-Wide Association Study Plus (MWAS+) approach to rigorously accelerate the identification of drugs with a high potential to be repurposed for delaying and preventing AD/ADRD: Step 1 is a hypothesis-free exploration; Step 2 is mechanistic filtering; And Step 3 is hypothesis testing using observational data and prospective cohort design. Our results demonstrated the feasibility of the MWAS+ approach. The Step 1 analysis identified potential candidate drugs including atorvastatin and GLP1. The literature search in Step 2 found evidence supporting the mechanistic plausibility of the statin-ADRD association. Finally, Step 3 confirmed our hypothesis that statin may lower the risk of incident ADRD, which was statistically significant using a target trial design that emulated randomized controlled trials.
开发一种新药或重新定位部分开发药物的高成本和时间促使人们对“药物再利用”产生了兴趣。药物再利用对于阿尔茨海默病（AD）或 AD 相关痴呆症（ADRD）特别有吸引力，因为对于 ADRD 没有不受限制的疾病修饰治疗方法。我们已经设计并试点测试了一种三步药物广泛关联研究加（MWAS+）方法，以严格加速确定具有高度潜力用于延缓和预防 AD/ADRD 的再利用药物：第 1 步是无假设的探索；第 2 步是机械过滤；第 3 步是使用观察性数据和前瞻性队列设计进行假设检验。我们的结果证明了 MWAS+方法的可行性。第 1 步分析确定了潜在的候选药物，包括阿托伐他汀和 GLP1。第 2 步的文献搜索发现了支持他汀类药物与 ADRD 关联的机制合理性的证据。最后，第 3 步证实了我们的假设，即他汀类药物可能降低 ADRD 的发病风险，这在使用模拟随机对照试验的目标试验设计时具有统计学意义。
Zotero 插件