A study by the Cleveland Clinic has found that sildenafil is a promising drug candidate to help prevent and treat Alzheimer’s disease.
Sildenafil is sold under the brand name Viagra and Revatio for the treatment of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), respectively.
The study, published in the Nature Aging Journal, used computational methodology to determine existing drugs as potential treatments for Alzheimer’s.
Analyzing a large-scale database of more than 7 million patients, the study found that sildenafil is associated with a 69% reduced incidence of Alzheimer’s, suggesting that a follow-up clinical trial is necessary to test the drug’s efficacy in patients with the neurological condition.
Lead author Dr. Feixiong Cheng of Cleveland Clinic’s Genomic Medicine Institute said, “Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself. Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.”
Dr. Cheng and his team have found that understanding subtypes (endophenotypes) of Alzheimer’s may help to reveal common underlying mechanisms, leading to the discovery of actionable targets for drug repositioning.
The accumulation of beta-amyloid and tau proteins in the brain is the hallmark of Alzheimer’s disease.
“Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself,” explained Dr. Cheng. “Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.”
He noted, “Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate.”
The authors found that sildenafil users were 69% less likely to develop Alzheimer’s disease than non-sildenafil users.
In addition, they found that sildenafil had a 55% reduced risk of Alzheimer’s compared to losartan, 63% compared to metformin, 65% compared to diltiazem, and 64% compared to glimepiride.
Dr. 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.”
“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 II randomized clinical trial to test causality and confirm sildenafil’s clinical benefits for Alzheimer’s patients,” he added. “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.”
