Cleveland Clinic research showed a 69% reduction in Alzheimer’s risk with the drug Viagra.
Alzheimer’s disease is the most common cause of dementia worldwide. In the United States, approximately 5.8 million people suffered from Alzheimer’s in 2020. This number is expected to rise further in the coming years. Therefore, scientists are on the search for effective new treatments for the neurological condition. This has led to the development of Alzheimer’s vaccines, currently under trial, and even a drug that targets amyloid-beta plaques within the brain. However, a team of Cleveland Clinic researchers took a different approach: drug repurposing. They looked at existing FDA-approved drugs, such as Viagra, for potential therapeutic properties for Alzheimer’s disease.
Using a large gene-mapping network, researchers sidelined candidates that could be an effective treatment for Alzheimer’s disease from a total of over 1,600 FDA-approved drugs. They looked at drugs that targeted beta-amyloid and tau proteins; buildup of the two proteins is a hallmark of Alzheimer’s disease. Thus, resulting in the discovery of Sildenafil.
Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself. Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.
Dr Feixiong Cheng, study author
Sildenafil, better known by the brand name Viagra, is a phosphodiesterase inhibitor that is an FDA-approved treatment for erectile dysfunction. The drug causes dilation of blood vessels and muscle relaxation around the lungs, heart, and genitals. According to the recent study, the drug can also disrupt the interaction between amyloid and tau proteins.
Phase II Trial in the Works
Using insurance claims data from over 7 million Americans, the team then analyzed Alzheimer’s disease outcomes among sildenafil users and non-users. Results showed that sildenafil users had a 69% lower risk of the disease as compared to non-users. Moreover, the drug had a 55% reduced Alzheimer’s risk compared to losartan, 63% compared to metformin, 64% compared to glimepiride and 65% compared to diltiazem.
The team also noted a reduced risk of Alzheimer’s in sildenafil users with comorbidities that typically increase the risk of disease. Such as hypertension, diabetes, and coronary heart disease. Researchers further demonstrated sildenafil’s therapeutic properties using patient-derived brain cells. Addition of the drug to the petri dish caused an increase in neuronal growth and decreased accumulation of tau proteins.
To further establish an association between sildenafil and Alzheimer’s risk, the team is now planning on conducting a phase II trial for the drug.
Reference:
Fang, J., Zhang, P., Zhou, Y. et al. Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer’s disease. Nat Aging 1, 1175–1188 (2021). https://doi.org/10.1038/s43587-021-00138-z
