Using artificial intelligence to identify anti-hypertensives as possible disease modifying agents in Parkinson's disease

Pharmacoepidemiol Drug Saf. 2021 Feb;30(2):201-209. doi: 10.1002/pds.5176. Epub 2020 Nov 30.


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 < 0.01) and angiotensin converting enzyme inhibitors (ACEi) and diuretics (HR = 0.60, p-value <0.01). Increased risk was observed with exposure to alpha-blockers alone (HR = 1.81, p < 0.001) and the combination of alpha-blockers and CCB (HR = 3.17, p < 0.05).

Conclusions: We present evidence that a computational approach can efficiently identify leads for disease-modifying drugs. We have identified the combination of ARBs and DHP-CCBs as of particular interest in PD.

Keywords: Parkinson disease; antihypertensive agents; artificial intelligence; epidemiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Antihypertensive Agents / adverse effects
  • Artificial Intelligence
  • Calcium Channel Blockers / therapeutic use
  • Humans
  • Hypertension* / diagnosis
  • Hypertension* / drug therapy
  • Hypertension* / epidemiology
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / epidemiology


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Calcium Channel Blockers