In a new study from Cleveland Clinic, researchers found sildenafil—an FDA-approved therapy for erectile dysfunction (Viagra) and pulmonary hypertension (Ravatio)—can be a promising drug candidate to help prevent and treat Alzheimer’s disease.
The team 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 7 million patients, they determined that sildenafil is associated with a 69% reduced incidence of Alzheimer’s disease.
Without the development of effective new treatments, Alzheimer’s disease is set to impact 13.8 million Americans by 2050, underscoring the need for rapid development of prevention and treatment strategies.
Drug repurposing—the use of an existing drug for new therapeutic purposes—offers a practical alternative to the costly and time-consuming traditional drug discovery process.
The buildup of beta-amyloid and tau proteins in the brain leads to amyloid plaques and tau neurofibrillary tangles—two hallmarks of Alzheimer’s-related brain changes.
The amount and location of these proteins in the brain may help define endophenotypes.
However, no FDA-approved, anti-amyloid or anti-tau small molecule Alzheimer’s treatments currently exist, with many clinical trials for such treatments have failed in the past decade.
In the study, the team 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.
They pinpointed drugs that target both amyloid and tau as having higher scores compared to drugs that target just one or the other.
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 7 million people in the U.S. 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% less likely to develop Alzheimer’s disease than non-sildenafil users after 6 years of follow-up.
Specifically, sildenafil had a 55% reduced risk of the disease compared to losartan, 63% compared to metformin, 65% compared to diltiazem and 64% compared to glimepiride.
Notably, the team found that sildenafil use reduced the likelihood of Alzheimer’s in individuals with coronary artery disease, high blood pressure and type 2 diabetes.
The findings establish an association between sildenafil use and reduced incidence of Alzheimer’s disease.
The team is now planning a mechanistic trial and a phase II randomized clinical trial to test causality and confirm sildenafil’s clinical benefits for Alzheimer’s patients.
If you care about Alzheimer’s disease, please read studies about why some older people less likely to have Alzheimer’s disease and findings of this daily habit that may help treat Alzheimer’s disease.
For more information about your health, please see recent studies about new discovery that could lead to new Alzheimer’s disease treatments and results showing that new drug for Alzheimer’s disease prevention found safe and effective.
The study is published in Nature Aging. One author of the study is Feixiong Cheng, Ph.D.
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