Alzheimer’s disease, the most common form of age-related dementia, affects hundreds of millions of people around the world. Despite the growing number of cases, there is currently no effective treatment. What if it already existed, but its use was until now reserved for another pathological condition? This is the hypothesis of scientists at the Cleveland Clinic about the sildenafil, a treatment approved by the Food and Drug Administration for erectile dysfunction (Viagra) and thepulmonary hypertension (Ravatio). Their study published in Nature Aging reveals that it could be a promising drug candidate to prevent and treat Alzheimer’s disease.
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Using a computer system and a genetic mapping network covering 7 million patients, the researchers wanted to determine which drug among the 1,600 molecules approved by the US health authority could prove to be an effective treatment for Alzheimer’s disease. They assigned higher scores to drugs targeting both beta-amyloid protein and tau protein. in the brain, two cerebral pathological phenomena described in Alzheimer’s disease, compared to drugs targeting only one or the other. The results put sildenafil at the top of the list of drugs to be tested in a future clinical trial.
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“Sildenafil significantly improves cognition and memory”
Researchers have already been able to determine than sildenafil is associated with a 69% reduced incidence of Alzheimer’s disease. “Studies show that the interaction between amyloid and tau protein contributes more to Alzheimer’s disease than either alone. », Explains Prof. Feixiong Cheng. “We hypothesized that drugs targeting the intersection of the molecular network of endophenotypes amyloid and tau should have the greatest potential for success. This is good news since the use of an already existing treatment for new therapeutic purposes offers an alternative to the development of new drugs, a very long and expensive process.
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« Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, has emerged as the best drug candidate. », Adds Professor Cheng. “We have found that its use reduced the likelihood of developing Alzheimer’s disease in people with coronary artery disease, hypertension and type 2 diabetes, all of which are co-morbidities significantly associated with the risk of the disease. To further explore the effect of sildenafil on Alzheimer’s disease, researchers developed a brain cell model derived from an affected patient. Alzheimer’s disease using stem cells.
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This experience made it possible to determine how including sildenafil may influence disease-related brain changes: this molecule increases the growth of brain cells and decreases the hyperphosphorylation of tau proteins, a characteristic that leads to neurofibrillary tangles that are found in Alzheimer’s disease. In addition to launching a clinical trial to confirm the clinical benefits of sildenafil in a large cohort of Alzheimer’s patients, the scientific team plans to apply this “drug reorientation” approach to other neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis.
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