Using artificial intelligence to identify anti‐hypertensives as possible disease modifying agents in Parkinson's disease
| Autor: | Scott Spangler, Sharon Hensley Alford, Lorraine V. Kalia, Italo Buleje, Piyush Madan, Alix M. B. Lacoste, Connie Marras, Yanyan Han, Naomi P. Visanji |
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| Rok vydání: | 2020 |
| Předmět: |
Drug
Oncology medicine.medical_specialty Parkinson's disease Multivariate analysis Epidemiology media_common.quotation_subject Angiotensin-Converting Enzyme Inhibitors Disease 030226 pharmacology & pharmacy Angiotensin Receptor Antagonists 03 medical and health sciences 0302 clinical medicine Artificial Intelligence Internal medicine medicine Humans Pharmacology (medical) 030212 general & internal medicine Antihypertensive Agents media_common biology business.industry Dihydropyridine Parkinson Disease Angiotensin-converting enzyme Calcium Channel Blockers medicine.disease Drug repositioning Hypertension Cohort biology.protein business medicine.drug |
| Zdroj: | Pharmacoepidemiology and Drug Safety. 30:201-209 |
| ISSN: | 1099-1557 1053-8569 |
| Popis: | PURPOSE 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-world data to investigate the association between exposure to highly ranked drugs and PD. METHODS Using IBM Watson for Drug Discoveryâ (WDD) we identified several antihypertensive drugs that may reduce aSyn oligomerization. Using IBM MarketScanâ 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-dependent covariate. Diuretics were used as the referent group. Age at hypertension diagnosis, sex, and several comorbidities were included in multivariate analyses. RESULTS 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-CCB) (HR = 0.55, p |
| Databáze: | OpenAIRE |
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