{"id":133226,"date":"2021-12-07T19:17:05","date_gmt":"2021-12-08T03:17:05","guid":{"rendered":"http:\/\/new.thepinetree.net\/?p=133226"},"modified":"2021-12-07T19:17:05","modified_gmt":"2021-12-08T03:17:05","slug":"cleveland-clinic-research-shows-drug-in-viagra-reduced-likelihood-of-developing-alzheimers-by-69","status":"publish","type":"post","link":"https:\/\/new.thepinetree.net\/?p=133226","title":{"rendered":"Cleveland Clinic Research Shows Drug in Viagra Reduced Likelihood of Developing Alzheimer\u2019s By 69%"},"content":{"rendered":"

Cleveland, OH…..A new Cleveland Clinic<\/a>-led study has identified sildenafil \u2013 an FDA-approved therapy for erectile dysfunction (Viagra) and pulmonary hypertension (Revatio) \u2013 as a promising drug candidate to help prevent and treat Alzheimer\u2019s disease.<\/p>\n

\"\"<\/a><\/p>\n

\"\"<\/a><\/p>\n

According to findings published in\u00a0Nature Aging<\/a><\/em>,<\/em>\u00a0the research team, led by\u00a0Feixiong Cheng, Ph.D<\/a>., of Cleveland Clinic\u2019s\u00a0Genomic Medicine Institute<\/a>, used computational methodology to screen and validate FDA-approved drugs as potential therapies for Alzheimer\u2019s disease. Through a large-scale analysis of a database of more than 7 million patients, they determined that sildenafil is associated with 69% reduced incidence of Alzheimer\u2019s disease, indicating the need for follow-up clinical trial testing of the drug\u2019s efficacy in patients with the disease.<\/p>\n

\n

.<\/em><\/p>\n<\/div>\n

Without the development of effective new treatments, Alzheimer\u2019s disease is set to impact 13.8 million Americans by 2050, underscoring the need for rapid development of prevention and treatment strategies. Drug repurposing \u2013 use of an existing drug for new therapeutic purposes \u2013 offers a practical alternative to the costly and time-consuming traditional drug discovery process.<\/p>\n

\u201cThis paper is an example of a growing area of research in precision medicine where big data is key to connecting the dots between existing drugs and a complex disease like Alzheimer\u2019s,\u201d said Jean Yuan, M.D., 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), which funded this research. \u201cThis is one of many efforts we are supporting to find existing drugs or available safe compounds for other conditions that would be good candidates for Alzheimer\u2019s disease clinical trials.\u201d<\/p>\n

Dr. Cheng\u2019s team has found that understanding subtypes (endophenotypes) of neurodegenerative diseases such as Alzheimer\u2019s disease may help to reveal common underlying mechanisms and lead to discovery of actionable targets for drug repurposing.<\/p>\n

The buildup of beta amyloid and tau proteins in the brain leads to amyloid plaques and tau neurofibrillary tangles \u2013 two hallmarks of Alzheimer\u2019s-related brain changes. The amount and location of these proteins in the brain may help define endophenotypes. However, no FDA-approved, anti-amyloid or anti-tau small molecule Alzheimer\u2019s treatments currently exist, with many clinical trials for such treatments having failed in the past decade.<\/p>\n

\u201cRecent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer\u2019s than either by itself,\u201d said Dr. Cheng. \u201cTherefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.\u201d<\/p>\n

Using a large gene-mapping network, researchers integrated genetic and other biologic data to determine which of over 1,600 FDA-approved drugs could be an effective treatment for Alzheimer\u2019s disease. They pinpointed drugs that target both amyloid and tau as having higher scores compared to drugs that target just one or the other. \u201cSildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate,\u201d said Dr. Cheng.<\/p>\n

The research team utilized a large database of claims data of more than 7 million people in the U.S. to examine the relationship between sildenafil and Alzheimer\u2019s disease outcomes by comparing sildenafil users to non-users. The analysis included patients using comparator drugs that either were in an active Alzheimer\u2019s clinical trial (losartan or metformin) or were not yet reported as relevant to the disease (diltiazem or glimepiride).<\/p>\n

They found that sildenafil users were 69% less likely to develop Alzheimer\u2019s disease than non-sildenafil users after 6 years of follow-up. Specifically, sildenafil had a 55% reduced risk of the disease compared to losartan, 63% compared to metformin, 65% compared to diltiazem and 64% compared to glimepiride.<\/p>\n

\u201cNotably, we found that sildenafil use reduced the likelihood of Alzheimer\u2019s 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,\u201d added Dr. Cheng.<\/p>\n

To further explore sildenafil\u2019s effect on Alzheimer\u2019s disease, the researchers developed an Alzheimer\u2019s patient-derived brain cell model using stem cells. In the model, they found that sildenafil increased brain cell growth and decreased hyperphosphorylation of tau proteins (a hallmark which leads to neurofibrillary tangles), offering biological insights into how sildenafil may influence disease-related brain changes.<\/p>\n

\u201cBecause our findings only establish an association between sildenafil use and reduced incidence of Alzheimer\u2019s disease, we are now planning a mechanistic trial and a phase II randomized clinical trial to test causality and confirm sildenafil\u2019s clinical benefits for Alzheimer\u2019s patients,\u201d said Dr. Cheng. \u201cWe also foresee our approach being applied to other neurodegenerative diseases, including Parkinson\u2019s disease and amyotrophic lateral sclerosis, to accelerate the drug discovery process.\u201d<\/p>\n

Jiansong Fang, Ph.D., a former research scholar in Dr. Cheng\u2019s lab; Pengyue Zhang, Ph.D., an assistant research professor at Indiana University School of Medicine; Yadi Zhou, Ph.D., a data scientist in Dr. Cheng\u2019s lab; and Chien-Wei Chiang, Ph.D., a research scientist at The Ohio State University College of Medicine, are co-first authors. Dr. Cheng presented the initial findings at the 2021 Alzheimer\u2019s Association International Conference. The study was supported by NIA, NIH grants R01AG066707 and R01AG066707-01S1, and the Translational Therapeutics Core of the Cleveland Alzheimer\u2019s Disease Research Center.<\/p>\n

About Cleveland Clinic<\/strong>
\nCleveland Clinic<\/a><\/u>\u00a0\u2013 now in its centennial year \u2013 is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many\u00a0medical breakthroughs<\/a><\/u>, including coronary artery bypass surgery and the first face transplant in the United States.\u00a0U.S. News & World Report<\/em>\u00a0consistently names Cleveland Clinic as one of the nation\u2019s best hospitals in its annual \u201cAmerica\u2019s Best Hospitals\u201d survey. Among Cleveland Clinic\u2019s 70,800 employees worldwide are more than 4,660 salaried physicians and researchers, and 18,500 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,500-bed health system that includes a 173-acre main campus near downtown Cleveland, 19 hospitals, more than 220 outpatient facilities, and locations in southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2020, there were 8.7 million total outpatient visits, 273,000 hospital admissions and observations, and 217,000 surgical cases throughout Cleveland Clinic\u2019s health system. Patients came for treatment from every state and 185 countries. Visit us at\u00a0clevelandclinic.org<\/a>.\u00a0Follow us at\u00a0twitter.com\/ClevelandClinic<\/a>. News and resources available at\u00a0newsroom.clevelandclinic.org<\/a>.<\/a><\/u><\/p>\n","protected":false},"excerpt":{"rendered":"

Cleveland, OH…..A new Cleveland Clinic-led study has identified sildenafil \u2013 an FDA-approved therapy for erectile dysfunction (Viagra) and pulmonary hypertension (Revatio) \u2013 as a promising drug candidate to help prevent and treat Alzheimer\u2019s disease. According to findings published in\u00a0Nature Aging,\u00a0the research team, led by\u00a0Feixiong Cheng, Ph.D., of Cleveland Clinic\u2019s\u00a0Genomic Medicine Institute, used computational methodology to […]<\/p>\n","protected":false},"author":1,"featured_media":133228,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_cbd_carousel_blocks":"[]","jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[20,33,1],"tags":[],"class_list":["post-133226","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-featured","category-health-fitness","category-news","last_archivepost"],"jetpack_featured_media_url":"https:\/\/new.thepinetree.net\/wp-content\/uploads\/2021\/12\/21-CCC-2569610-AlzheimersDisease-1920x1080_rev-768x432-1.jpg","jetpack_sharing_enabled":true,"jetpack-related-posts":[],"_links":{"self":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/posts\/133226","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=133226"}],"version-history":[{"count":1,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/posts\/133226\/revisions"}],"predecessor-version":[{"id":133229,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/posts\/133226\/revisions\/133229"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/media\/133228"}],"wp:attachment":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=133226"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=133226"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=133226"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}