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A large-scale study in the journal Nature Aging has identified sildenafil – otherwise known by its brand name Viagra – as a potential candidate for the treatment and prevention of Alzheimer’s disease (AD). After analyzing insurance claims data from more than seven million people in the US, the study authors noted that claimants who received sildenafil were almost 70 percent less likely to develop AD than those who did not use the drug.
Viagra belongs to a class of medications known as phosphodiesterase inhibitors, which promote the dilation of blood vessels and cause the relaxation of muscles in and around the heart, lungs, and genitals. It is most commonly used to treat erectile dysfunction and pulmonary hypertension, although prior research has hinted at a possible role for phosphodiesterase inhibitors in the treatment of dementia.
The study authors began by analyzing the biological underpinnings of AD in order to identify 13 different genetically controlled physiological mechanisms – or endophenotypes – that are associated with the disease. In total, these 13 endophenotypes were found to be dependent upon the interactions between 351,444 different protein interactions.
The most significant of these interactions was that between amyloid and tau proteins, both of which are known to accumulate in the brain of Alzheimer’s patients, and are considered to be a major driver of the disease.
“Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself,” explained study author Dr Feixiong Cheng in a statement. “Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.”
The researchers therefore examined the impact of over 1,600 FDA-approved drugs on the various proteins involved with AD, and found that sildenafil was the most effective at disrupting the interaction between amyloid and tau proteins.
Building on this finding, they assessed insurance claims made by 7.2 million people, revealing that Viagra users were 69 percent less likely than non-users to be diagnosed with Alzheimer’s within six years of taking the drug. Unsurprisingly, the majority of claimants who took the drug were men, although the authors state that their finding held true even after adjusting for sex, age, and race.
Finally, the team used stem cells from an AD patient in order to generate neurons in a petri dish, and noted that the addition of sildenafil sparked increased neuronal growth and inhibited the accumulation of tau proteins. While this observation points towards a possible mechanism for the drug’s ability to protect against Alzheimer’s, the researchers insist that their study does not establish causality and that more work is needed in order to confirm the efficacy of Viagra for the treatment of AD.
“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,” said Cheng.
“We also foresee our approach being applied to other neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis, to accelerate the drug discovery process.”
