Medication-Wide Association Study Plus (MWAS+): A Proof of Concept Study on Drug Repurposing.
Medication-Wide Association Study Plus (MWAS+): A Proof of Concept Study on Drug Repurposing.
复制标题
DOI：
10.3390/medsci10030048
复制
发表时间：
2022-08-31
期刊：
影响因子：
--
通讯作者：
Zeng-Treitler Q
中科院分区：
文献类型：
--
作者：
Cheng Y;Zamrini E;Ahmed A;Wu WC;Shao Y;Zeng-Treitler Q
开发一种新药或重新定位一种部分开发的药物所需的高昂成本和时间激发了人们对“重新调整”药物用途的兴趣。药物再利用对阿尔茨海默病(AD)或AD相关痴呆(ADRD)特别感兴趣，因为ADRD没有不受限制的疾病修改治疗方法。我们设计并试行了一种三步药物全关联研究加(MWAS+)方法，以严格加快识别具有高潜力的药物，以延缓和预防AD/ADRD：第一步是无假设的探索；第二步是机械筛选；第三步是使用观察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。步骤2中的文献搜索发现了支持他汀类药物-ADRD关联的机制合理性的证据。最后，步骤3证实了我们的假设，即他汀类药物可以降低发生ADRD的风险，这在模拟随机对照试验的目标试验设计中具有统计学意义。
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.
登录
查看更多内容
他汀类药物治疗对老年人认知能力下降和事件痴呆的影响。
影响因子：
24
作者：
Zhou Z;Ryan J;Ernst ME;Zoungas S;Tonkin AM;Woods RL;McNeil JJ;Reid CM;Curtis AJ;Wolfe R;Wrigglesworth J;Shah RC;Storey E;Murray A;Orchard SG;Nelson MR;ASPREE Investigator Group
通讯作者：
ASPREE Investigator Group
DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
5
作者：
Hernan, Miguel A.;Robins, James M.
通讯作者：
Robins, James M.
影响因子：
6.1
作者：
Li HH;Lin CL;Huang CN
通讯作者：
Huang CN
DOI：
10.1016/j.trci.2019.05.008
发表时间：
2019-01-01
影响因子：
4.8
作者：
Cummings, Jeffrey;Lee, Garam;Zhong, Kate
通讯作者：
Zhong, Kate