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Study Supports Repurposing Erectile Dysfunction Drug for Alzheimer’s

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New Cleveland Clinic-led research points to sildenafil (Viagra) as a potential treatment for Alzheimer’s disease. The study provides evidence from computational models, insurance claims data and observations from brain cells in Alzheimer’s patients.   

Sildenafil is the main component of drugs used to treat erectile dysfunction (Viagra) and pulmonary arterial hypertension (Revatio). 

“Our findings provide further weight to re-purposing this existing FDA-approved drug as a novel treatment for Alzheimer’s, which is in great need of new therapies,” said Feixiong Cheng, Ph.D., who led the research. “We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil’s potential against this devastating neurological disease.” 

Alzheimer’s disease currently affects over 6 million Americans and incidence is expected to triple by 2050, underscoring the need for rapid development of new prevention and treatment strategies. 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. 

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Published in Journal of Alzheimer’s Disease, the study builds upon the researchers’ earlier findings in 2021 that used computational models to initially identify sildenafil as a promising drug candidate to help prevent and treat Alzheimer’s disease.  

In the new study, Dr. Cheng, director of the  Cleveland Clinic Genome Center, and his team analyzed millions of de-identified insurance claims from two independent patient databases, which revealed a 30-54% reduced prevalence in Alzheimer’s disease diagnoses among patients who took sildenafil compared to those who did not after adjusting various possible confounding factors.  

In brain cells from Alzheimer’s patients, researchers also showed that sildenafil lowers levels of neurotoxic tau proteins, which are known to be associated with Alzheimer’s disease when they build up. They also found that neurons treated with sildenafil expressed genes related to cell growth, improved brain function, reduced inflammation and other processes known to protect against the neural degeneration associated with Alzheimer’s disease.  

Dr. Cheng’s findings demonstrate the feasibility of using computer models to identify potential new drug candidates in a fast, reliable way, representing a significant step forward in Alzheimer’s drug discovery.  

“After integrating this large amount of data computationally, it is rewarding to see sildenafil’s effects in human neurons and real-world patient outcomes,” said Dr. Cheng. “We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease.”  

Reference: Gohel D, Zhang P, Gupta AK, et al. 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. J Alzheimers Dis. 2024. doi: 10.3233/JAD-231391

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