Findings published in Nature Aging show 69% reduced likelihood of developing the disease
NASSAU, BAHAMAS — A new Cleveland Clinic-led study has identified sildenafil, an FDA-approved therapy for erectile dysfunction (Viagra) and pulmonary hypertension (Revatio), as a promising drug candidate to help prevent and treat Alzheimer’s disease — a disease that is gradually increasing in The Bahamas.
According to findings published in Nature Aging, the research team, led by Dr Feixiong Cheng, PhD, of Cleveland Clinic’s Genomic Medicine Institute, used computational methodology to screen and validate FDA-approved drugs as potential therapies for Alzheimer’s disease.
Through a large-scale analysis of a database of more than seven million patients, they determined that sildenafil is associated with 69 percent reduced incidence of Alzheimer’s disease, indicating the need for follow-up clinical trial testing of the drug’s efficacy in patients with the disease.
The research was funded by the National Institute on Aging (NIA), a division of the National Institutes of Health (NIH).
Dr Jean Yuan, MD, PhD, program director of Translational Bioinformatics and Drug Development at NIA, said: “This paper is an example of a growing area of research in precision medicine, where big data is key to connecting the dots between existing drugs and a complex disease like Alzheimer’s.
“This is one of many efforts we are supporting to find existing drugs or available safe compounds for other conditions that would be good candidates for Alzheimer’s disease clinical trials.”
Using a large gene-mapping network, researchers integrated genetic and other biologic data to determine which of over 1,600 FDA-approved drugs could be an effective treatment for Alzheimer’s disease.
Cheng said: “Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate.”
The research team utilized a large database of claims data of more than seven million people in the US to examine the relationship between sildenafil and Alzheimer’s disease outcomes by comparing sildenafil users to non-users.
They found that sildenafil users were 69 percent less likely to develop Alzheimer’s disease than non-sildenafil users after six years of follow-up.
Cheng said: “Notably, we found that sildenafil use reduced the likelihood of Alzheimer’s in individuals with coronary artery disease, hypertension and Type 2 diabetes, all of which are comorbidities significantly associated with risk of the disease, as well as in those without.”
He added: “Because our findings only establish an association between sildenafil use and reduced incidence of Alzheimer’s disease, we are now planning a mechanistic trial and a phase two randomized clinical trial to test causality and confirm sildenafil’s clinical benefits for Alzheimer’s patients.
“We also foresee our approach being applied to other neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis, to accelerate the drug discovery process.”
Jiansong Fang, PhD, a former research scholar in Cheng’s lab; Pengyue Zhang, PhD, an assistant research professor at Indiana University School of Medicine; Yadi Zhou, PhD, a data scientist in Cheng’s lab; and Chien-Wei Chiang, PhD, a research scientist at the Ohio State University College of Medicine, are co-first authors.
Cheng presented the initial findings at the 2021 Alzheimer’s Association International Conference. The study was supported by NIA, NIH grants R01AG066707 and R01AG066707-01S1 and the Translational Therapeutics Core of the Cleveland Alzheimer’s Disease Research Center.
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