NIH-funded research reveals clinical trial candidate for those with genetic risk.

Food and Drug Administration may be a potential candidate for an Alzheimer’s disease treatment for those who are at genetic risk, according to findings published in Nature Aging.

The research included analysis showing that those who took bumetanide — a commonly used and potent diuretic — had a significantly lower prevalence of Alzheimer’s 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 a precision medicine approach 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 Alzheimer’s.

Knowing that one of the most significant genetic risk factors for late-onset Alzheimer’s is a form of the apolipoprotein E gene called APOE4, researchers analyzed data derived from 213 brain tissue samples and identified the Alzheimer’s gene expression signatures, the levels to which genes are turned on or off, specific to APOE4 carriers.

The strongest candidate was bumetanide, 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 Alzheimer’s and induced pluripotent stem cell-derived human neurons.

The analysis showed that those who had the genetic risk and took bumetanide had a ~35% to 75% lower prevalence of Alzheimer’s disease compared to those not taking the drug.

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

federal government effort to conduct and support research on aging and the health and well-being of older people

Taubes A et al. Experimental and real world evidence supporting the computational repurposing of bumetanide to prevent or treat APOE4-related Alzheimer’s disease. Nature Aging