Ageing: Sildenafil as a candidate drug for Alzheimer’s disease

Prescription of sildenafil — a drug used to treat pulmonary hypertension and erectile dysfunction — is associated with a substantial reduction in the risk of developing Alzheimer’s disease, according to a study published in Nature Aging. These findings suggest that repurposed sildenafil may be a therapeutic option for this disease.

Alzheimer’s disease (AD) is the most common form of age-related dementia, affecting hundreds of millions of people worldwide. There is currently no effective treatment for AD, which, as a result of population aging, leads to large and growing financial and disease burdens on society.

Using a computational approach, Feixiong Cheng colleagues integrated genetic and other biological data to build 13 disease ‘endophenotype modules’ that capture the biological signatures of AD. These modules were mapped onto a large network of 351,444 human protein–protein interactions. Network proximity scores were then generated for over 1,600 FDA-approved drugs, with a higher score indicating that a drug physically interacts with multiple molecular targets within AD-related modules. Sildenafil was assigned one of the top scores, suggesting that it might influence AD. To test this, the authors analysed insurance claims data from over seven million people in the US, revealing that the prescription of sildenafil was significantly associated with a 69% reduction in the risk of AD diagnosis after 6 years of follow-up. Potential influential factors such as sex, race and age were adjusted for, with the former being particularly important as sildenafil is mainly used to treat erectile dysfunction in men.

The authors caution that their study design cannot demonstrate a causal relationship between use of a particular drug and risk of AD. Randomized, clinical trials involving both sexes with a placebo control are therefore needed to determine sildenafil’s efficacy in this context.