Precision medicine data dive shows water pill may be viable to test as Alzheimer’s treatment – The Highland County Press

A commonly available oral diuretic pill approved by the U.S. Food and Drug Administration may be a potential candidate for an Alzheimers disease treatment for those who are at genetic risk, according to findings published inNature Aging.

The research included analysis showing that those whotook bumetanide a commonly used andpotent diuretic had a significantly lower prevalence of Alzheimers disease compared to those not taking the drug. The study, funded by the National Institute on Aging (NIA), part of the National Institutes of Health, advances aprecision medicineapproach for individuals at greater risk of the disease because of their genetic makeup.

The research team analyzed information in databases of brain tissue samples and FDA-approved drugs, performed mouse and human cell experiments and explored human population studies to identify bumetanide as a leading drug candidate that may potentially be repurposed to treat Alzheimers.

Though further tests and clinical trials are needed, this research underscores the value of big data-driven tactics combined with more traditional scientific approaches to identify existing FDA-approved drugs as candidates for drug repurposing to treat Alzheimers disease, said NIA Director Richard J. Hodes, M.D.

Knowing that one of the most significantgenetic risk factors for late-onset Alzheimers is a form of the apolipoprotein E gene called APOE4, researchers analyzed data derived from 213 brain tissue samples and identified the Alzheimers gene expression signatures, the levels to which genes are turned on or off, specific to APOE4 carriers. Next, they compared the APOE4-specific Alzheimers signatures against those of more than 1,300 known FDA-approved drugs.

Five drugs emerged with a gene expression signature that the researchers believed might help neutralize the disease. The strongest candidate wasbumetanide, which is used to treat fluid retention often caused by medical problems such as heart, kidney and liver disease.

The researchers validated the data-driven discoveries by testing bumetanide in both mouse models of Alzheimers andinduced pluripotent stem cell-derived human neurons. Researchers found that treating mice which expressed the human APOE4 gene reduced learning and memory deficits.

The neutralizing effects were also confirmed in the human cell-based models, which led to the hypothesis that people already taking bumetanide should have lower rates of Alzheimers. To test this, the team pared down electronic health record data sets from more than 5 million people to two groups: adults over 65 who took bumetanide and a matching group who did not take bumetanide. The analysis showed that those who had the genetic risk and took bumetanide had a ~35-percent to 75-percent lower prevalence of Alzheimers disease compared to those not taking the drug.

We know that Alzheimers disease will likely require specific types of treatments, perhaps multiple therapies, including some that may target an individuals unique genetic and disease characteristics much like cancer treatments that are available today, said Jean Yuan, M.D., Ph.D., Translational Bioinformatics and Drug Development program director in the NIA Division of Neuroscience. The data in this paper make a good case to conduct a proof-of-concept trial of bumetanide in people with genetic risk.

The research team was led by scientists at Gladstone Institutes, San Francisco, the University of California, San Francisco and the Icahn School of Medicine at Mount Sinai, New York City. This group is one of more than 20 teams supported by NIA through aprogramencouraging the researcher community to seek, through big data approaches, drugs that could potentially be repurposed.

The research was funded by NIH grants R01AG057683, R01AG048017, F31AG058439, R01AG061150, F31AG057150, R21TR001743 and K01ES028047.

NIA leads NIHs systematic planning, development and implementation ofresearch milestonesto achieve the goal of effectively treating and preventing Alzheimers and related dementias. This research is related to Milestone7.B, Initiate research programs for translational bioinformatics and network pharmacology to support rational drug repositioning and combination therapy from discovery through clinical development.

For more information about NIH and its programs, visitwww.nih.gov.

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Precision medicine data dive shows water pill may be viable to test as Alzheimer's treatment - The Highland County Press