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New study suggests Viagra could be used to treat Alzheimer’s disease

March 14, 2024

New Cleveland Clinic-led research showed that sildenafil (Viagra) could be a potential treatment for Alzheimer’s disease. The study, published on March 1 in the Journal of Alzheimer’s Disease, builds upon earlier research from the same team that initially identified the drug’s potential as a candidate to treat the devastating neurodegenerative disease. The latest study provides evidence from computational models, insurance claims data, and observations from brain cells in Alzheimer’s patients that all indicate the drug’s potential against the disease. (Gohel, 2024)

What’s the potential patient impact?

According to the Alzheimer’s Association, AD currently affects more than 6 million Americans and the incidence is expected to triple by 2050. With no known cure available, the idea of drug repurposing is compelling and offers an expedient alternative to the costly and time-consuming traditional drug discovery process.

What does the evidence show?

Feixoion Cheng, PhD, inaugural director of the Cleveland Clinic Genome Center, and his team specialize in systems biology and multi-omics research and previously identified a connection between sildenafil and AD. Findings from that study were published in 2021 in the journal Nature Aging.

In their latest study, the investigators used real-world patient data from the MarketScan Medicare Supplemental and Clinformatics databases. They included individuals with pharmacy claims for sildenafil and four drug compactor cohorts, including bumetanide, furosemide, spironolactone, and nifedipine. The analysis showed that sildenafil use was associated with a reduced likelihood of AD relative to the control drugs. Specifically, sildenafil was associated with a 54% reduced incidence of AD in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of AD in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared to spironolactone.

Additionally, to visualize the mechanics of the drug in patients with AD, the team performed dish experiments using neurons from four different patients, two of whom developed the condition sporadically and two of whom had an inherited form of AD. They found that neurons treated with sildenafil appeared to have lower levels of phosphorylated tau proteins, a key pathologic feature of AD. They also observed that neurons treated with sildenafil expressed genes related to neuron generation, neuroplasticity, neural function, neural inflammation, and other processes known to protect against neural degeneration. (Cleveland Clinic, 2024; Gohel, 2024)

What’s next?

Previous studies into the relationship between sildenafil and AD have found contradictory effects. While Cheng’s 2021 study found a 69% lower risk of AD among sildenafil users, a Harvard study that same year found no protective effect in patients with pulmonary hypertension. It remains unclear whether sildenafil and similar drugs influence AD. In Cheng’s most recent study, the team concluded that while their real-world patient data validation and mechanistic observations suggest that while sildenafil is potentially a repurposable drug for AD, randomized clinical trials are necessary to validate the causal treatment effects of the drug. (Amenabar, 2024; Gohel, 2024)

Sources:

(2024, March 4). Cleveland Clinic. Cleveland Clinic-led research supports repurposing sildenafil (Viagra) for Alzheimer’s treatment. https://newsroom.clevelandclinic.org/2024/03/05/cleveland-clinic-led-research-supports-repurposing-sildenafil-viagra-for-alzheimers-treatment/

Amenabar, T. (2024, February 22). The Washington Post. Why Viagra has been linked with better brain health. https://www.washingtonpost.com/wellness/2024/02/22/viagra-alzheimers-dementia-erectile-dysfunction/

Gohel D, et al. (2024, March 1). J Alzheimers Dis. 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. https://pubmed.ncbi.nlm.nih.gov/38427489/