Candidate Drug for Alzheimer’s Disease


Cleveland Clinic Research Identifies Sildenafil as Candidate Drug for Alzheimer’s Disease

Findings published in Nature Aging show 69% reduced likelihood of developing the disease

A new Cleveland Clinic-led study has identified sildenafil – an FDA-approved therapy for erectile dysfunction (Viagra) and pulmonary hypertension (Revatio) – as a promising drug candidate to help prevent and treat Alzheimer’s disease.

According to findings published in Nature Aging, the research team, led by Feixiong Cheng, Ph.D., of Cleveland Clinic’s Genomic Medicine Institute, used computational methodology to screen and validate FDA-approved drugs as potential therapies for Alzheimer’s 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’s disease, indicating the need for follow-up clinical trial testing of the drug’s efficacy in patients with the disease.

Feixiong Cheng, Ph.D.

 

 

 

 

 

 

 

 

 

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

“This 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’s,” 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. “This 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’s disease clinical trials.”

Dr. Cheng’s team has found that understanding subtypes (endophenotypes) of neurodegenerative diseases such as Alzheimer’s disease may help to reveal common underlying mechanisms and lead to discovery of actionable targets for drug repurposing.

The buildup of beta amyloid and tau proteins in the brain leads to amyloid plaques and tau neurofibrillary tangles – two hallmarks of Alzheimer’s-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’s treatments currently exist, with many clinical trials for such treatments having failed in the past decade.

“Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself,” said Dr. Cheng. “Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success.”

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