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Viagra Is Promising Drug Candidate To Help Prevent and Treat Alzheimer’s Disease

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Cleveland Clinic analysis identifies sildenafil as candidate drug for Alzheimer’s illness.

Findings printed in Nature Growing older present 69% lowered chance of creating the illness.

A brand new Cleveland Clinic-led examine has recognized sildenafil – an FDA-approved remedy for erectile dysfunction (Viagra) and pulmonary hypertension (Ravatio) – as a promising drug candidate to assist forestall and deal with Alzheimer’s illness.

Based on findings printed in Nature Growing older, the analysis workforce, led by Feixiong Cheng, Ph.D., of Cleveland Clinic’s Genomic Medication Institute, used computational methodology to display and validate FDA-approved medication as potential therapies for Alzheimer’s illness. By way of a large-scale evaluation of a database of greater than 7 million sufferers, they decided that sildenafil is related to 69% lowered incidence of Alzheimer’s illness, indicating the necessity for follow-up scientific trial testing of the drug’s efficacy in sufferers with the illness.

“Latest research present that the interaction between amyloid and tau is a better contributor to Alzheimer’s than both by itself,” mentioned Dr. Cheng. “Subsequently, we hypothesized that medication focusing on the molecular community intersection of amyloid and tau endophenotypes ought to have the best potential for achievement.”

With out the event of efficient new therapies, Alzheimer’s illness is ready to impression 13.8 million People by 2050, underscoring the necessity for speedy growth of prevention and remedy methods. Drug repurposing – use of an current drug for brand spanking new therapeutic functions – provides a sensible different to the pricey and time-consuming conventional drug discovery course of.

Based on findings printed in Nature Growing older, the analysis workforce, led by Feixiong Cheng, Ph.D., of Cleveland Clinic’s Genomic Medication Institute, decided that sildenafil is related to 69% lowered incidence of Alzheimer’s illness. Credit score: Cleveland Clinic

“This paper is an instance of a rising space of analysis in precision drugs the place massive information is vital to connecting the dots between current medication and a fancy illness like Alzheimer’s,” mentioned Jean Yuan, M.D., Ph.D., program director of Translational Bioinformatics and Drug Growth on the Nationwide Institute on Growing older (NIA), a part of the Nationwide Institutes of Well being (NIH), which funded this analysis. “That is one among many efforts we’re supporting to search out current medication or accessible protected compounds for different situations that may be good candidates for Alzheimer’s illness scientific trials.”

Dr. Cheng’s workforce has discovered that understanding subtypes (endophenotypes) of neurodegenerative ailments akin to Alzheimer’s illness might assist to disclose widespread underlying mechanisms and result in discovery of actionable targets for drug repurposing.

The buildup of beta amyloid and tau proteins within the mind results in amyloid plaques and tau neurofibrillary tangles – two hallmarks of Alzheimer’s-related mind modifications. The quantity and location of those proteins within the mind might assist outline endophenotypes. Nevertheless, no FDA-approved, anti-amyloid or anti-tau small molecule Alzheimer’s therapies at the moment exist, with many scientific trials for such therapies having failed prior to now decade.

“Latest research present that the interaction between amyloid and tau is a better contributor to Alzheimer’s than both by itself,” mentioned Dr. Cheng. “Subsequently, we hypothesized that medication focusing on the molecular community intersection of amyloid and tau endophenotypes ought to have the best potential for achievement.”

Utilizing a big gene-mapping community, researchers built-in genetic and different biologic information to find out which of over 1,600 FDA-approved medication might be an efficient remedy for Alzheimer’s illness. They pinpointed medication that concentrate on each amyloid and tau as having larger scores in comparison with medication that concentrate on only one or the opposite. “Sildenafil, which has been proven to considerably enhance cognition and reminiscence in preclinical fashions, offered as the very best drug candidate,” mentioned Dr. Cheng.

The analysis workforce utilized a big database of claims information of greater than 7 million individuals within the U.S. to look at the connection between sildenafil and Alzheimer’s illness outcomes by evaluating sildenafil customers to non-users. The evaluation included sufferers utilizing comparator medication that both have been in an lively Alzheimer’s scientific trial (losartan or metformin) or weren’t but reported as related to the illness (diltiazem or glimepiride).

They discovered that sildenafil customers have been 69% much less prone to develop Alzheimer’s illness than non-sildenafil customers after 6 years of follow-up. Particularly, sildenafil had a 55% lowered danger of the illness in comparison with losartan, 63% in comparison with metformin, 65% in comparison with diltiazem and 64% in comparison with glimepiride.

“Notably, we discovered that sildenafil use lowered the chance of Alzheimer’s in people with coronary artery illness, hypertension, and sort 2 diabetes, all of that are comorbidities considerably related to danger of the illness, in addition to in these with out,” added Dr. Cheng.

To additional discover sildenafil’s impact on Alzheimer’s illness, the researchers developed an Alzheimer’s patient-derived mind cell mannequin utilizing stem cells. Within the mannequin, they discovered that sildenafil elevated mind cell development and decreased hyperphosphorylation of tau proteins (an indicator that results in neurofibrillary tangles), providing organic insights into how sildenafil might affect disease-related mind modifications.

“As a result of our findings solely set up an affiliation between sildenafil use and lowered incidence of Alzheimer’s illness, we are actually planning a mechanistic trial and a section II randomized scientific trial to check causality and verify sildenafil’s scientific advantages for Alzheimer’s sufferers,” mentioned Dr. Cheng. “We additionally foresee our method being utilized to different neurodegenerative ailments, together with Parkinson’s illness and amyotrophic lateral sclerosis, to speed up the drug discovery course of.”

Reference: “Endophenotype-based in silico community drugs discovery mixed with insurance coverage document information mining identifies sildenafil as a candidate drug for Alzheimer’s illness” 6 December 2021, Nature Growing older.
DOI: 10.1038/s43587-021-00138-z

Jiansong Fang, Ph.D., a former analysis scholar in Dr. Cheng’s lab; Pengyue Zhang, Ph.D., an assistant analysis professor at Indiana College Faculty of Medication; Yadi Zhou, Ph.D., an information scientist in Dr. Cheng’s lab; and Chien-Wei Chiang, Ph.D., a analysis scientist at The Ohio State College School of Medication, are co-first authors. Dr. Cheng offered the preliminary findings on the 2021 Alzheimer’s Affiliation Worldwide Convention. The examine was supported by NIA, NIH grants R01AG066707 and R01AG066707-01S1, and the Translational Therapeutics Core of the Cleveland Alzheimer’s Disease Analysis Heart.

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