Study finds sildenafil a candidate drug for Alzheimer’s disease

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A new study from the Cleveland Clinic has found that sildenafil, an FDA-approved treatment for erectile dysfunction and pulmonary hypertension, is a promising drug candidate to help prevent and treat Alzheimer’s disease. The research has been published in the “Nature Aging Journal”.

According to the results, the research team, led by Feixiong Cheng, Ph.D., of the Genomic Medicine Institute at the Cleveland Clinic, used a computational methodology to screen and validate drugs approved by the FDA as potential therapies for Alzheimer’s disease. Through a large-scale analysis of a database of over 7 million patients, they determined that sildenafil is associated with a 69% reduced incidence of Alzheimer’s disease, indicating the need for follow-up clinical trials on the effectiveness of the drug in patients with the disease.

“Recent studies show that the interaction between amyloid and the tau protein contributes more to Alzheimer’s disease than either alone. Therefore, we hypothesized that drugs targeting the intersecting the molecular network of amyloid and tau endophenotypes are expected to have the greatest potential for success, “said Dr Cheng. Without the development of new effective treatments, Alzheimer’s disease is expected to affect 13.8 million Americans by 2050, underscoring the need to rapidly develop prevention and treatment strategies. Drug reorientation – using an existing drug for new therapeutic purposes – offers a practical alternative to the costly and time-consuming traditional process of drug discovery.

“This article is an example of a growing area of ​​research in precision medicine where big data is essential for connecting the dots between existing drugs and a complex disease like Alzheimer’s disease,” said Jean Yuan, MD, Ph.D., program director of Translational Bioinformatics and Drug Development at the National Institute on Aging (NIA), part of the National Institutes of Health (NIH), who funded this research. “This is one of many efforts we are supporting to find existing drugs or safe compounds available for other conditions that would be good candidates for clinical trials in Alzheimer’s disease,” Yuan added.

Dr Cheng’s team discovered that understanding the subtypes (endophenotypes) of neurodegenerative diseases such as Alzheimer’s disease can help reveal common underlying mechanisms and lead to the discovery of workable targets for reorientation of disease. medications. The build-up of beta-amyloid and tau proteins in the brain leads to the formation of amyloid plaques and tau neurofibrillary tangles, two hallmarks of brain changes associated with Alzheimer’s disease. The amount and location of these proteins in the brain can help define endophenotypes. However, no FDA approved small molecule anti-amyloid or anti-tau therapy currently exists, with many clinical trials for such treatments having failed over the past decade.

“Recent studies show that the interaction between amyloid and the tau protein contributes more to Alzheimer’s disease than either alone. Therefore, we hypothesized that drugs targeting the intersecting the molecular network of amyloid and tau endophenotypes are expected to have the greatest potential for success, “said Dr Cheng. Using a large network of genetic mapping, researchers integrated genetic and other biological data to determine which of the more than 1,600 FDA-approved drugs could be an effective treatment for Alzheimer’s disease. They identified drugs targeting both amyloid and tau as having higher scores than drugs targeting either.

“Sildenafil, which has been shown to dramatically improve cognition and memory in preclinical models, has emerged as the best drug candidate,” said Dr Cheng. The research team used a large database of claims from over 7 million people in the United States 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 who were part of an active clinical trial in Alzheimer’s disease (losartan or metformin) or had not yet been reported as relevant for the disease (diltiazem or glimepiride). .

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 reduced risk of 55% compared to losartan, 63% compared to metformin, 65% compared to diltiazem and 64% compared to glimepiride. “In particular, we found that the use of sildenafil reduced the likelihood of developing Alzheimer’s disease in people with coronary heart disease, hypertension, and type 2 diabetes, all of which are co-morbidities significantly associated with risk. disease, as well as in those who do not have it, ”added Dr. Cheng. .

To further explore the effect of sildenafil on Alzheimer’s disease, researchers developed a brain cell model derived from a patient with Alzheimer’s disease using stem cells. In the model, they found that sildenafil increased brain cell growth and decreased tau protein hyperphosphorylation (a characteristic that leads to neurofibrillary tangles), offering biological information on how sildenafil can influence brain changes. disease-related. “Because our results uniquely establish an association between the use of sildenafil and a reduced incidence of Alzheimer’s disease, we now plan a mechanistic trial and a phase II randomized clinical trial to test the causality and confirm the clinical benefits of the drug. sildenafil for patients with Alzheimer’s disease. We also anticipate that our approach will be applied to other neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis, to speed up the drug discovery process, ”said Dr. Cheng. (ANI)

(This story was not edited by Devdiscourse staff and is auto-generated from a syndicated feed.)

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