Dr. Susan Kohlhaas On Whether Viagra Can Reduce the Risk of Alzheimer’s

PDE-5 inhibitors like Viagra ushered in a new era in treatments for erectile dysfunction (ED); now, researchers may have discovered a surprising new use for the drugs. There is evidence that Viagra could help stem the onset of Alzheimer’s disease.

A study looking at the potential of repurposing licensed drugs for the treatment of Alzheimer’s disease has identified the erectile dysfunction drug sildenafil, brand name Viagra, as a candidate for future analysis.

Since it has been determined that the root cause of Alzheimer’s dementia is a build-up of specific amyloid proteins in the brain, research has focused on drugs that can break up or slow that build-up of plaque. Numerous trials have been undertaken to test drugs that may be able to do so. 

From the early 2000s until last year, most have shown limited promise. While the qualified approval of the anti-amyloid monoclonal antibody aducanumab provides some hope that research into Alzheimer’s is at least aiming in the right direction, the immense cost and serial failure of prior trials have led to companies and academics examining alternative routes to drug development. One of these options is based on finding already-approved compounds that may be repurposed for Alzheimer’s disease, which brings us to PDE-5 inhibitors like Viagra.

Viagra, approved in the US in 1998 and patented by Pfizer, is an artificial compound that was originally designed to treat cardiovascular disease. The drug did little to treat angina, but its unexpected and enervating side effects made it a worldwide success.

The team of researchers, who published their findings in the journal Nature, first used Artificial Intelligence-driven biomolecular computer models to identify Viagra as a top contender to treat amyloid build-up. To verify their data, the team then looked at the insurance claims and medical histories of men that were regular Viagra users. Based on those records, they were astonished to discover that  Viagra was associated with a 69% reduction in the risk of Alzheimer’s diagnosis in the following six years since beginning to take the drug for ED. 

To examine what molecular mechanisms might explain this, the team dosed neurons in a dish derived from the stem cells of Alzheimer’s disease patients, showing that the ED drug indeed increased the growth of neural connections and reduced the accumulation of amyloid protein.

However, The promise of these findings is a qualified one. The computational approach taken was not capable of establishing causality, meaning there was no way to conclusively say that taking Viagra reduced the risk of Alzheimer’s disease in the insurance claim cohort.

Another significant factor is Viagra’s somewhat specialized indication. Only 2% of people claiming for the drug were women, who make up the majority of the Alzheimer’s disease patient population. Dr. Susan Kohlhaas, director of research at Alzheimer’s Research UK, who was not involved in the study, said in a press release: “While the researchers did look at the effect of sildenafil on females, there isn’t enough information to be able to accurately draw conclusions about its effect in females.

Kohlhaas also addressed the need for future experiments to back up the paper. “The researchers have conducted lab-based experiments to give an indication as to why the drug may impact diseases like Alzheimer’s, but these early-stage experiments would need follow-up in more thorough tests,” she said.