A new study by the Cleveland Clinic has found that sildenafil, an FDA-approved therapy for erectile dysfunction and pulmonary hypertension, is a promising drug candidate to help prevent and treat Alzheimer’s disease. The research team, led by Feixiong Cheng, Ph.D., 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 7 million patients, they determined that sildenafil is associated with a 69 per cent 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. “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 end phenotypes should have the greatest potential for success,” said Dr Cheng.
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. 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,” said Dr Cheng. 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. The analysis included patients using comparator drugs that either were in an active Alzheimer’s clinical trial or were not yet reported as relevant to the disease.