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Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer’s disease

UnHope20

December 12, 2021

2 upvotes

/r/Male_Studies

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Post Information

Title	Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer’s disease
Author	UnHope20
Upvotes	2
Comments	1
Date	December 12, 2021 11:50 PM UTC (4 years ago)
Subreddit	Posted in /r/Male_Studies
Original Link	https://old.reddit.com/r/Male_Studies/comments/rf1p6f/endophenotypebased_in_silico_network_medicine/
Archive Link	https://theredarchive.com/r/Male_Studies/endophenotype-based-in-silico-network-medicine.1216103 https://theredarchive.com/post/1216103

Comments

[–]UnHope20[S] 1 point2 points3 points 4 years ago (0 children) | Copy Link

We developed an endophenotype disease module-based methodology for Alzheimer’s disease (AD) drug repurposing and identified sildenafil as a potential disease risk modifier.

Based on retrospective case–control pharmacoepidemiologic analyses of insurance claims data for 7.23 million individuals, we found that sildenafil usage was significantly associated with a 69% reduced risk of AD (hazard ratio 0.31, 95% confidence interval 0.25–0.39, P < 1.0 × 10–8).

Propensity score-stratified analyses confirmed that sildenafil is significantly associated with a decreased risk of AD across all four drug cohorts tested (diltiazem, glimepiride, losartan and metformin) after adjusting for age, sex, race and disease comorbidities.

We also found that sildenafil increases neurite growth and decreases phospho-tau expression in neuron models derived from induced pluripotent stem cells from patients with AD, supporting mechanistically its potential beneficial effect in AD.

The association between sildenafil use and decreased incidence of AD does not establish causality, which will require a randomized controlled trial.