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“‘Sildenafil (Viagra)’ reduces the risk of Alzheimer’s” – Sciencetimes

In a new study recently led by the Cleveland Clinic in the US, sildenafil, approved by the US Food and Drug Administration (FDA) for the treatment of erectile dysfunction (trade name: Viagra) and pulmonary hypertension (trade name: Labatio), helps prevent and treat Alzheimer’s disease. has been identified as a promising drug candidate.

Cleveland Clinic’s Gene Medicine Research Institute, Dr. Feixiong Cheng’s team used a computer analysis method to select and verify Alzheimer’s disease-treatable drugs among FDA-approved drugs.Nature Aging) was announced on the 6th.

In a large-scale analysis of a database of more than 7 million patients, the researchers found that sildenafil reduced the risk of Alzheimer’s disease by 69%. This indicates the need for clinical trials to see how effective this drug is in Alzheimer’s disease patients.

Sildenafil 100mg packaged drug prescribed in Europe. © WikiCommons/Lupus in Saxonia

Seeking to change the use of existing drugs rather than new drugs that are slow in development

“Recent studies have shown that the interaction between amyloid and tau proteins has a greater effect on the development of Alzheimer’s disease than the individual proteins themselves,” said Dr. Cheng. “We hypothesized that drugs that target cross-molecular networks of

Unless effective new treatments are developed, the disease is expected to affect 13.8 million patients in the United States alone by 2050, necessitating rapid development of preventive and therapeutic strategies.

According to data from the National Statistical Office in Korea, one in 10 people over the age of 65 suffers from dementia, and as the elderly population increases, the number of patients is expected to continue to increase.

However, developing an effective drug through the traditional drug discovery process is costly and time-consuming. Therefore, repurposing existing drugs into new disease treatments may be a viable alternative.

A diagram showing the process by which beta-amyloid plaques are made in the brain. © WikiCommons/NIA

Dr. Jean Yuan, director of the Intermediate Bioinformatics and New Drug Development Program at the National Institute of Aging (NIA) under the National Institutes of Health (NIH) said, “This paper is an example of a growing area in precision medicine research. “It shows that this is the key to bridging the dots between drugs and complex diseases like Alzheimer’s.”

He added that this study is one of many NIA efforts to support the discovery of safe compounds that can be used or existing drugs that may be good candidates for clinical trials in Alzheimer’s disease.

Targeting both amyloid and tau

Dr. Cheng’s team confirmed that understanding the subtypes (endophenotypes) of neurodegenerative diseases such as Alzheimer’s disease can reveal common underlying mechanisms and help uncover viable targets for drug repurposing.

Figure showing the process of tau nerve fiber entanglement in the brain. © WikiCommons/NIA

Accumulation of beta-amyloid and tau proteins in the brain results in amyloid plaques and tau neurofibrillary tangles. These are two hallmarks of Alzheimer’s-associated brain changes. The amount and location of these proteins in the brain can help define the endogenous phenotype.

However, despite numerous clinical trials conducted over the past decade, no FDA-approved anti-amyloid or anti-tau small molecule Alzheimer’s treatment has yet emerged.

The team used a large-scale gene mapping network to integrate genetic and other biological data and to determine which of more than 1,600 FDA-approved drugs were effective against Alzheimer’s disease.

They found drugs that targeted both proteins and scored higher than drugs that targeted either amyloid or tau alone. “Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, is the best drug candidate,” said Dr. Cheng.

Peychon Cheng, PhD, Cleveland Clinic Institute of Genetic Medicine, USA, who led the study. Dr. Cheng’s team reported that sildenafil was found to reduce the risk of Alzheimer’s by 69%. © Cleveland Clinic

Sildenafil users are 69% less likely to develop the disease than non-users

The researchers investigated the relationship between sildenafil and Alzheimer’s disease by comparing sildenafil users and non-users using large medical billing data from more than 7 million Americans.

The analysis also included patients undergoing clinical trials for Alzheimer’s disease (losartan or metformin) or using an unrelated comparator (diltiazem or glimepiride).

After six years of follow-up, the researchers found that sildenafil users were 69% less likely to develop Alzheimer’s than those who did not use sildenafil. Sildenafil had a 55% lower risk of Alzheimer’s than losartan, 63% lower than metformin, 65% lower than diltiazem, and 64% lower than glimepiride.

“In this study, we found that the use of sildenafil specifically reduced the incidence of Alzheimer’s disease in people with and without diabetes mellitus, high blood pressure and type 2 diabetes,” said Dr. Cheng.

A paper published on the 6th of ‘Nature Aging’. © SPRINGER NATURE / Nature Aging

Development and experimentation of Alzheimer’s brain cell model with stem cells

To further investigate the effects of sildenafil on Alzheimer’s disease, the research team developed a brain cell model derived from Alzheimer’s patients using stem cells.

In this model, they found that sildenafil promoted brain cell growth and decreased hyperphosphorylation of the tau protein, which causes nerve fiber entanglement. This provides biological insight into how sildenafil affects Alzheimer’s-related brain changes.

“Since the results of this study only established an association between sildenafil use and a reduced incidence of Alzheimer’s disease, this study was randomized with the current mechanistic trial to test causality and confirm the clinical benefit of sildenafil in Alzheimer’s patients,” said Dr. We are planning a phase 2 clinical trial.”

“Our approach is expected to be applied to these diseases as well to accelerate the drug development process for other neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis (Lou Gehrig’s disease),” he said.

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