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Press release
Monday, October 11, 2021
NIH-funded research reveals clinical trial candidate for people with genetic risk.
According to the results published in Natural aging. The research included analysis showing that those who took bumetanide – a potent and commonly used diuretic – had a significantly lower prevalence of Alzheimer’s disease compared to those who did not take the drug. The study, funded by the National Institute on Aging (NIA), part of the National Institutes of Health, offers a precision medicine approach for those most at risk of contracting the disease due to their genetic makeup.
The research team analyzed information from databases of brain tissue samples and FDA-approved drugs, performed experiments on mice and human cells, and explored human population studies for identify bumetanide as a prominent drug candidate that could potentially be reused to treat Alzheimer’s disease.
“While more clinical trials and trials are needed, this research underscores the value of big data-based tactics combined with more traditional scientific approaches to identify existing drugs approved by the FDA as candidates for drug reuse for treat Alzheimer’s disease, “said NIA Director Richard J. Hodes, MD
Knowing that one of the most important genetic risk factors for late-onset Alzheimer’s disease is a form of the apolipoprotein E gene called APOE4, the researchers analyzed data from 213 brain tissue samples. and identified the Alzheimer’s disease gene expression signatures, the levels at which genes are transformed. enabled or disabled, specific to APOE4 carriers. Next, they compared the Alzheimer’s signatures specific to APOE4 to those of more than 1,300 known drugs approved by the FDA. Five drugs have emerged with a gene expression signature that the researchers say could help neutralize the disease. The strongest candidate was bumetanide, which is used to treat fluid retention often caused by medical conditions such as heart, kidney and liver disease.
The researchers validated the findings based on the data by testing bumetanide in mouse models of Alzheimer’s disease and human neurons derived from induced pluripotent stem cells. The researchers found that treating mice expressing the human APOE4 gene reduced learning and memory deficits. The neutralizing effects have also been confirmed in human cell-based models, which has led to the hypothesis that people already taking bumetanide should have lower rates of Alzheimer’s disease. To test this, the team narrowed down electronic health records data sets of over 5 million people to two groups: adults over 65 who took bumetanide and a corresponding group who did not. taken bumetanide. The analysis showed that those who were at genetic risk and took bumetanide had a 35% to 75% lower Alzheimer’s disease prevalence compared to those who did not take the drug.
“We know that Alzheimer’s disease is likely to require specific types of treatments, perhaps multiple therapies, including some that can target an individual’s unique genetic and pathological characteristics, much like cancer treatments that are available today, “said Jean Yuan, MD, Ph.D., program director for Translational Bioinformatics and Drug Development in the Neuroscience Division of the NIA. “The data in this article makes the case for a proof-of-concept trial of bumetanide in people at genetic risk.”
The research team was led by scientists from the Gladstone Institutes in San Francisco, the University of California at San Francisco, and the Icahn School of Medicine at Mount Sinai, New York. This group is one of more than 20 teams supported by the NIA as part of a program encouraging the research community to search, through big data approaches, for drugs that could potentially be reused.
The research was funded by NIH grants R01AG057683, R01AG048017, F31AG058439, R01AG061150, F31AG057150, R21TR001743 and K01ES028047.
The NIA leads the systematic planning, development and implementation of the NIH research milestones to achieve the goal of effectively treating and preventing Alzheimer’s disease and related dementias. This research is related to Milestone 7.B, “Initiate translational bioinformatics and network pharmacology research programs to support rational drug repositioning and combination therapy from discovery to clinical development. “
About the National Institute of Aging (NIA): NIA is leading the US federal government’s effort to conduct and support research on aging and the health and well-being of older adults. Learn more about age-related cognitive changes and neurodegenerative diseases through the NIA’s Alzheimer’s Disease and Related Dementia Education and Reference Center (ADEAR) website. Visit the NIA’s main website for information on a range of aging topics, in English and Spanish, and stay connected.
About the National Institutes of Health (NIH):The NIH, the national agency for medical research, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the principal federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.
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