Erectile dysfunction drug Viagra could have a key role in the prevention and treatment of Alzheimer’s disease, a new study has revealed.
And through analysis of more than seven million patients, the Cleveland Clinic study has revealed that the drug is associated with a 69 per cent reduction in incidence of Alzheimer’s.
“Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself,” said Dr Feixiong Cheng, of Cleveland Clinic’s Genomic Medicine Institute, who led the research team.
“Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.”
In the study, it was established that sildenafil (Viagra) users were 69 per cent less likely to develop Alzheimer’s disease than non-sildenafil users after six years of follow-up.
Specifically, sildenafil had a 55 per cent reduced risk of the disease compared to losartan, 63 per cent compared to metformin, 65 per cent compared to diltiazem and 64 per cent compared to glimepiride.
Drug repurposing – use of an existing drug for new therapeutic purposes – offers a practical alternative to the costly and time-consuming traditional drug discovery process, and could support the millions of people living with Alzheimer’s globally in accessing treatments more quickly.
Dr Cheng’s team has found that understanding subtypes (endophenotypes) of neurodegenerative diseases such as Alzheimer’s disease may help to reveal common underlying mechanisms and lead to discovery of actionable targets for drug repurposing.
The buildup of beta amyloid and tau proteins in the brain leads to amyloid plaques and tau neurofibrillary tangles – two hallmarks of Alzheimer’s-related brain changes. The amount and location of these proteins in the brain may help define endophenotypes.
However, no FDA-approved, anti-amyloid or anti-tau small molecule Alzheimer’s treatments currently exist, with many clinical trials for such treatments having failed in the past decade.
Dr Feixiong Cheng
Using a large gene-mapping network, researchers integrated genetic and other biologic data to determine which of over 1,600 FDA-approved drugs could be an effective treatment for Alzheimer’s disease.
They pinpointed drugs that target both amyloid and tau as having higher scores compared to drugs that target just one or the other.
“Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate,” said Dr Cheng.
“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.”
“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,” said Dr Jean Yuan, program director of Translational Bioinformatics and Drug Development at the National Institute on Aging (NIA), part of the National Institutes of Health (NIH), which funded this research.
“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.”
A phase II randomised clinical trial is now being planned to advance the study, as well as the approach also being applied to other neurodegenerative conditions.
