Viagra Could Be Good for Your Brain

Can Viagra prevent or reverse Alzheimer’s disease? Older men’s ship may be coming in. New research from the Cleveland Clinic suggests the erectile-dysfunction drug could ward off cognitive decline, illustrating how artificial intelligence can help scientists repurpose old medications for new diseases.

The study, published this month in the Journal of Alzheimer’s Disease, builds on earlier research by the Cleveland Clinic that identified sildenafil, the generic name for Viagra, as a promising Alzheimer’s treatment.

Researchers first identified genes associated with the disease’s pathology, amyloid plaque and tau tangles in the brain. They then mapped out the molecular interplay among more than 1,600 drugs already approved by the Food and Drug Administration and Alzheimer’s-related proteins. After identifying 66 medications that interact with Alzheimer’s genes and pathology, they settled on sildenafil as the one with the most potential.

As a next step, they analyzed insurance claims from more than seven million Americans. They found that people who took sildenafil were 69% less likely to develop Alzheimer’s than those who didn’t after adjusting for sex, age and other diseases. Correlation doesn’t prove causation, but further study suggested they might be on to something.

Researchers grew neurons from the stem cells of Alzheimer’s patients in test tubes and exposed them to sildenafil. What do you know? The drug increased brain cell growth and decreased toxic tau, which usually develops in the early to middle stages of the disease. This suggested possible mechanisms by which sildenafil might arrest the disease.

In their new study, Cleveland Clinic researchers analyzed two patient databases and found that those who took sildenafil were 30% to 54% less likely to be diagnosed with Alzheimer’s. They also found that sildenafil activated genes in neurons that are associated with cell growth, improved brain function and reduced inflammation.

“We used artificial intelligence to integrate data across multiple domains, which all indicated sildenafil’s potential against this devastating neurological disease,” Feixiong Cheng, lead researcher at the Cleveland Clinic, explained.

It’s doubtful that Viagra explains why men suffer from Alzheimer’s at much lower rates than women, which has been true since before the drug was approved. And no, older men shouldn’t rush to ask their doctor for a prescription. Placebo-controlled trials are needed to prove its efficacy, since observational and test-tube studies don’t always bear out.

But the Cleveland Clinic’s research shows how AI can accelerate drug discovery and identify medications that can be put to new uses. Models can map and pinpoint connections among the drugs, genes, molecules and diseases. They can also help ferret out links between diseases and the medications in health records.

Scientists have typically stumbled on new uses for existing drugs by happenstance. 

Pfizer 

originally developed sildenafil to treat hypertension and angina, not male sexual dysfunction. Yet some patients in its clinical trials reported a surprising side effect: erections. One reason is that the drug dilates blood vessels and increases blood flow throughout the body. Viagara may improve cognition in the same way.

Similarly, scientists at Upjohn developed minoxidil, commonly known by the brand name Rogaine, as a pill to treat ulcers in the late 1950s. It didn’t work, but they discovered that it had a positive effect on blood pressure. More studies found that men on the hypertension drug also became hairier, which prompted trials into whether it could also treat male hair loss.

Eureka, the first medicine for baldness was born. Upjohn reformulated minoxidil into a topical treatment that carries fewer side effects than the blood-pressure medication, although dermatologists sometimes prescribe the pill off-label at low doses for men who don’t see results from the spray-on foam.

The antimalaria drug hydroxychloroquine was repurposed to treat rheumatoid arthritis and lupus after soldiers with the autoimmune diseases who received it during World War II showed improvements in their symptoms.

Or take the class of diabetes and obesity drugs known as GLP-1 agonists, which mimic a natural hormone that has been found to stimulate insulin, slow digestion and reduce appetite. GLP-1 drugs appear to work by activating certain receptors on cells that are most commonly found in the pancreas and brain but also in the kidney and liver.

Studies suggest that the drugs activate neural connections that control inflammation. Researchers are studying whether GLP-1 agonists could be used to treat kidney, liver, neurological and inflammatory diseases including depression, Alzheimer’s and Parkinson’s. 

Novo Nordisk

 is already testing its GLP-1 drugs in early-stage Alzheimer’s patients.

Diseases typically have diverse causes, and medications work in diverse ways. Scientists have typically taken many years, if not decades, to figure these out. One of AI’s great promises is that it will enable researchers to connect these dots in warp speed, cutting down on development time for new drugs and rapidly putting existing ones to new uses. Who knows? Maybe a Viagra-Ozempic combo could be a cure for Alzheimer’s.