Sildenafil may be new therapeutic option for Patients with Alzheimer's Disease: Study

A recent study by Dhruva Gohel unveiled promising evidence that support the use of sildenafil (Viagra), a phosphodiesterase-5 inhibitor which is commonly used in the treatment of erectile dysfunction, as a therapeutic option for Alzheimer's disease. The key findings were published in the recent issue of the Journal of Alzheimer’s Disease.

This comprehensive analysis used real-world patient data from extensive databases, including MarketScan® Medicare Supplemental and Clinformatics®. This study found compelling evidence linking sildenafil use to a reduced likelihood of developing Alzheimer's disease, after adjusting for various factors such as age, sex, race and comorbidities.

Their findings revealed that sildenafil usage was linked with a significant decrease in the incidence and prevalence of Alzheimer's disease across multiple drug comparison groups. When compared to spironolactone, sildenafil showed a remarkable 54% reduction of Alzheimer's disease risk in the MarketScan® database and a 30% decrease in prevalence in the Clinformatics® dataset.

Furthermore, this study analyzed the molecular mechanisms underlying the potential therapeutic effects of sildenafil. This research demonstrated that sildenafil treatment led to a dose-dependent reduction in tau hyperphosphorylation by utilizing induced pluripotent stem cells (iPSCs) derived from both familial and sporadic Alzheimer's disease patients.

The RNA-sequencing analysis of sildenafil-treated Alzheimer's disease patient iPSC-derived neurons revealed that sildenafil specifically targeted the Alzheimer's disease-related genes and pathways which provide mechanistic insights into its beneficial effects. These findings suggest that sildenafil could be repurposed as a treatment for Alzheimer’s disease, however, further randomized clinical trials are imperative to validate the causal treatment effects of sildenafil in Alzheimer's disease.

Source:

Gohel, D., Zhang, P., Gupta, A. K., Li, Y., Chiang, C.-W., Li, L., Hou, Y., Pieper, A. A., Cummings, J., & Cheng, F. (2024). Sildenafil as a Candidate Drug for Alzheimer’s Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons. In Journal of Alzheimer’s Disease (pp. 1–15). IOS Press. https://doi.org/10.3233/jad-231391