Viagra – Alzheimers disease

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

Researches 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. They 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/viagra/revatio use and decreased incidence of AD does not establish causality, which will require a randomized controlled trial.

The researchers began by identifying genes associated with AD pathology. Then they constructed a network of molecular interactions connecting these genes. They focused on the subset of genes associated with both amyloid plaques and tau tangles, instead of one or the other. They also constructed networks of drugs and their molecular targets for more than 1,600 FDA-approved drugs. Then they calculated the relationships between each drug’s targets and the AD network components.

The team identified 66 drugs with the closest relationships to AD-associated genes. Many are already being tested in ongoing AD clinical trials, proving the soundness of the approach. After considering other factors, the top candidate was sildenafil, also known by the brand names Viagra and Revatio. Sildenafil is FDA-approved to treat erectile dysfunction and pulmonary hypertension.

Next, the team analyzed insurance claims data from more than 7 million Americans. They found that the people (mostly men) who took sildenafil were 69% less likely to develop AD over 6 years than those who did not take the drug. This association between sildenafil and AD held after adjusting for sex, age, and other diseases and conditions.

To understand how sildenafil might affect AD, the researchers grew neurons from stem cells derived from AD patients. Exposing the cells to sildenafil led to increased growth of neurites, which connect neurons to each other, and decreased tau phosphorylation, an early biomarker of AD.

Taken together, these results show an association between sildenafil use and reduced AD risk. But the researchers emphasize that they haven’t shown that sildenafil prevents or reverses AD. There may be other factors responsible for the association.

“Because our findings only establish an association between sildenafil use and reduced incidence of Alzheimer’s disease, we are now planning a mechanistic trial and a phase II randomized clinical trial to test causality and confirm sildenafil’s clinical benefits for Alzheimer’s patients,” Cheng explains.

“This is one of many efforts we are supporting to find existing drugs or available safe compounds for other conditions that would be good candidates for Alzheimer’s disease clinical trials,” says Dr. Jean Yuan, a program director at NIA. Repurposing existing drugs could save time and costs of bringing AD therapies to patients.

If you take sildenafil (Viagra, Revatio) to treat erectile dysfunction or pulmonary arterial hypertension, here’s good news: the little blue or white pill may also be protecting you from Alzheimer’s disease. Researchers analyzed insurance claims data of 7.23 million people and found sildenafil users were 69% less likely to develop Alzheimer’s over a six-year period than non-users. The possible link? As part of the study, the researchers also examined brain cells from Alzheimer’s patients and found sildenafil users had more brain cell growth and slower formation of neurofibrillary tangles in the brain, an early biomarker of Alzheimer’s.

It’s important to note that the results showed only an association between sildenafil use and lower Alzheimer’s risk. Randomized controlled studies are needed to confirm the findings. But so far, it looks like sildenafil could have far-reaching health benefits.

References and sources


https://www.health.harvard.edu/mens-health/erectile-dysfunction-drug-may-lower-alzheimers-risk

https://www.nih.gov/news-events/nih-research-matters/viagra-associated-reduced-risk-alzheimers-disease

https://www.nature.com/articles/s43587-021-00138-z