{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:24:49Z","timestamp":1792801489640,"version":"4.5.0"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008914","name":"Ontario Brain Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008914","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Drug repurposing is an effective means of increasing treatment options for diseases, however identifying candidate molecules for the indication of interest from the thousands of approved drugs is challenging. We have performed a computational analysis of published literature to rank existing drugs according to predicted ability to reduce alpha synuclein (aSyn) oligomerization and analyzed real\u2010world data to investigate the association between exposure to highly ranked drugs and PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using IBM Watson for Drug Discovery\u00e2 (WDD) we identified several antihypertensive drugs that may reduce aSyn oligomerization. Using IBM MarketScan\u00e2 Research Databases we constructed a cohort of individuals with incident hypertension. We conducted univariate and multivariate Cox proportional hazard analyses (HR) with exposure as a time\u2010dependent covariate. Diuretics were used as the referent group. Age at hypertension diagnosis, sex, and several comorbidities were included in multivariate analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Multivariate results revealed inverse associations for time to PD diagnosis with exposure to the combination of the combination of angiotensin receptor II blockers (ARBs) and dihydropyridine calcium channel blockers (DHP\u2010CCB) (HR = 0.55,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and angiotensin converting enzyme inhibitors (ACEi) and diuretics (HR = 0.60,<jats:italic>p<\/jats:italic>\u2010value &lt;0.01). Increased risk was observed with exposure to alpha\u2010blockers alone (HR = 1.81,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and the combination of alpha\u2010blockers and CCB (HR = 3.17,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We present evidence that a computational approach can efficiently identify leads for disease\u2010modifying drugs. We have identified the combination of ARBs and DHP\u2010CCBs as of particular interest in PD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5176","type":"journal-article","created":{"date-parts":[[2020,11,21]],"date-time":"2020-11-21T11:08:21Z","timestamp":1605956901000},"page":"201-209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Using artificial intelligence to identify anti\u2010hypertensives as possible disease modifying agents in Parkinson's disease"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5968-7845","authenticated-orcid":false,"given":"Naomi P.","family":"Visanji","sequence":"first","affiliation":[{"name":"Edmond J. 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