An exciting find: Sildenafil a potential drug candidate to prevent Alzheimer’s disease

Sildenafil (Viagra) could potentially lower a person’s risk for Alzheimer’s disease, according to studies carried out by researchers at the Cleveland Clinic’s Genomic Medicine Institute. Their computational approach suggests that sildenafil may physically interact with biological factors that contribute to Alzheimer’s disease, a finding supported by an analysis of insurance claims that showed that sildenafil prescription was associated with a 69% reduced risk of developing Alzheimer’s disease. Dr. Feixiong Cheng (PhD) and colleagues used a computational model to screen what medications might interact with Alzheimer’s disease. The results showed sildenafil may physically interact with biological mechanisms present in Alzheimer’s disease, and influence the progression of the disease. “Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself,” said Dr. Cheng in a press release from the Cleveland Clinic. “Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.” The researchers went on to analyze American insurance claims data from 7.23 million people. A prescription of sildenafil was significantly associated with a 69% reduced risk of having a diagnosis of Alzheimer’s disease after six years of follow-up, compared to no prescription for sildenafil. The reduced risk associated with sildenafil remained even when the data was adjusted for age, sex and race; and when patients with coronary artery disease, hypertension, type 2 diabetes and mild cognitive impairment were both excluded from the analysis and included. “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,” Dr. Cheng said. When sildenafil was compared to prescriptions for other medications, it had a 55% reduced risk of Alzheimer’s disease compared to losartan, a 63% reduced risk compared to metformin, a 65% reduced risk compared to diltiazem and a 64% reduced risk compared to glimepride. Read: Controversial Alzheimer’s drug highlights concerns about Health Canada approval process The researchers explored potential mechanisms of action by conducting cell studies, including one experiment in neurons derived from stem cells from patients with Alzheimer’s disease. Sildenafil increased neurite growth and decreased hyperphosphorylation of tau proteins, which offered insights on how the drug may affect Alzheimer’s disease. The study design does not confirm a causal relationship between sildenafil. Further studies are needed, including randomized clinical trials involving both sexes, to determine if sildenafil reduces the risk of Alzheimer’s disease, the authors write in the paper in Nature Aging. “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,” said Dr. Cheng. “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.” Read: Pre-clinical research on new imaging technique looks to improve speed of diagnosis for neurological diseases

An exciting find: Sildenafil a potential drug candidate to prevent Alzheimer’s disease

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