PMID- 37274099
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240421
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Drug repurposing for reducing the risk of cataract extraction in patients with 
      diabetes mellitus: integration of artificial intelligence-based drug prediction 
      and clinical corroboration.
PG  - 1181711
LID - 10.3389/fphar.2023.1181711 [doi]
LID - 1181711
AB  - Diabetes mellitus (DM) increases the incidence of age-related cataracts. 
      Currently, no medication is approved or known to delay clinical cataract 
      progression. Using a novel approach based on AI, we searched for drugs with 
      potential cataract surgery-suppressing effects. We developed a drug discovery 
      strategy that combines AI-based potential candidate prediction among 2650 Food 
      and Drug Administration (FDA)-approved drugs with clinical corroboration 
      leveraging multicenter electronic health records (EHRs) of approximately 800,000 
      cataract patients from the TriNetX platform. Among the top-10 AI-predicted 
      repurposed candidate drugs, we identified three DM diagnostic ICD code groups, 
      such as cataract patients with type 1 diabetes mellitus (T1DM), type 2 diabetes 
      mellitus (T2DM), or hyperglycemia, and conducted retrospective cohort analyses to 
      evaluate the efficacy of these candidate drugs in reducing the risk of cataract 
      extraction. Aspirin, melatonin, and ibuprofen were associated with a reduced 5-, 
      10-, and 20-year cataract extraction risk in all types of diabetes. 
      Acetylcysteine was associated with a reduced 5-, 10-, and 20-year cataract 
      extraction risk in T2DM and hyperglycemia but not in T1DM patient groups. The 
      suppressive effects of aspirin, acetylcysteine, and ibuprofen waned over time, 
      while those of melatonin became stronger in both genders. Thus, the four 
      repositioned drugs have the potential to delay cataract progression in both 
      genders. All four drugs share the ability to directly or indirectly inhibit 
      cyclooxygenase-2 (COX-2), an enzyme that is increased by multiple cataractogenic 
      stimuli.
CI  - Copyright (c) 2023 Gao, Gorenflo, Kaelber, Monnier and Xu.
FAU - Gao, Zhenxiang
AU  - Gao Z
AD  - Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case 
      Western Reserve University, Cleveland, OH, United States.
FAU - Gorenflo, Maria
AU  - Gorenflo M
AD  - Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case 
      Western Reserve University, Cleveland, OH, United States.
AD  - Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, 
      Cleveland, OH, United States.
FAU - Kaelber, David C
AU  - Kaelber DC
AD  - The Center for Clinical Informatics Research and Education, The Metro Health 
      System, Cleveland, OH, United States.
FAU - Monnier, Vincent M
AU  - Monnier VM
AD  - Department of Pathology and Biochemistry, School of Medicine, Case Western 
      Reserve University, Cleveland, OH, United States.
FAU - Xu, Rong
AU  - Xu R
AD  - Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case 
      Western Reserve University, Cleveland, OH, United States.
LA  - eng
GR  - P30 EY011373/EY/NEI NIH HHS/United States
GR  - UM1 TR004528/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20230518
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10232753
OTO - NOTNLM
OT  - acetylcysteine
OT  - aging
OT  - aspirin
OT  - cataract surgery
OT  - ibuprofen
OT  - melatonin
OT  - pharmacological prevention
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/06/05 13:04
MHDA- 2023/06/05 13:05
PMCR- 2023/05/18
CRDT- 2023/06/05 11:57
PHST- 2023/03/14 00:00 [received]
PHST- 2023/05/05 00:00 [accepted]
PHST- 2023/06/05 13:05 [medline]
PHST- 2023/06/05 13:04 [pubmed]
PHST- 2023/06/05 11:57 [entrez]
PHST- 2023/05/18 00:00 [pmc-release]
AID - 1181711 [pii]
AID - 10.3389/fphar.2023.1181711 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 May 18;14:1181711. doi: 10.3389/fphar.2023.1181711. 
      eCollection 2023.