Viagra, a medicine best known for treating erectile dysfunction, may soon have a surprise new purpose: Alzheimer’s disease prevention. According to a trial of current FDA-approved drugs, using the treatment reduced the risk of having the condition by 69 percent over the next six years.
Sildenafil – which drug manufacturers label as Viagra for erectile dysfunction and as Revatio for pulmonary hypertension – emerged from a field of over 1,600 FDA-approved drugs as the most promising candidate to battle Alzheimer’s. Researchers from the Cleveland Clinic’s Genomic Medicine Institute examined a database of more than seven million patients, finding that the ED medication performed significantly better than high blood pressure and diabetes drugs like losartan and metformin.
Estimates predict that cases of Alzheimer’s disease, the most common form of dementia, will rise to just under 14 million in the United States by 2050. With no cure at the moment, scientists are turning to existing medications that may have dual benefits and save both time and money in designing a new drug.
“This paper is an example of a growing area of research in precision medicine where big data is key to connecting the dots between existing drugs and a complex disease like Alzheimer’s,” says Jean Yuan, M.D., Ph.D., from National Institutes of Health (NIH), in a media release. “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.”
Viagra targets both hallmarks of Alzheimer’s development
The Cleveland team, led by Dr. Feixiong Cheng, believes that understanding the subtypes (or endophenotypes) of neurodegenerative diseases like Alzheimer’s will help reveal the underlying triggers of these conditions. That would likely expose certain targets that scientists could focus on and find medications which act on these weaknesses.
When it comes to the brain changes Alzheimer’s causes, there are two main hallmarks of the disease. The first is a buildup of beta-amyloid and tau proteins in the brain. The second sees those buildups turn into amyloid plaques and tau neurofibrillary tangles. Currently, there are no FDA-approved medications that fight the buildup of beta-amyloid or tau proteins.
“Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself,” Dr. Cheng says. “Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.”
Using a large gene-mapping network, the team studied hundreds of FDA-approved drugs to find the ones which can target both amyloid and tau proteins. They then scored those candidates higher than other drugs capable of just targeting one.
“Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate,” Dr. Cheng reports.
Better protection than blood pressure medications
Researchers looked at the connection between Alzheimer’s disease onset and sildenafil among users and non-users over a follow-up period of six years. Compared to other drugs, sildenafil led to 55-percent lower risk of Alzheimer’s in comparison to taking losartan. The drug led to a 63-percent lower Alzheimer’s risk compared to metformin, a 64-percent lower risk than taking glimepiride, and a 65-percent lower risk compared to taking diltiazem.
Overall, compared to non-users of Viagra, taking the drug resulted in a 69-percent drop in the risk of dementia onset over the course of the study.
“Notably, we found that sildenafil use reduced the likelihood of Alzheimer’s in individuals with coronary artery disease, hypertension and type 2 diabetes, all of which are comorbidities significantly associated with risk of the disease, as well as in those without,” Dr. Cheng adds.
Additionally, the team created an Alzheimer’s brain cell model using stem cells to see how sildenafil impacts dementia onset in a lab experiment. They found that sildenafil increases brain cell growth while also decreasing the hyperphosphorylation of tau proteins – a key process that creates the neurofibrillary tangles.
“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,” Dr. Cheng concludes. “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.”
