November 8, 2021
A drug that has been used for decades to treat fluid buildup in the body showed promise in preventing Alzheimer’s onset in those who are at high genetic risk of developing the disease, according to a new report. More research is needed to assess its potential benefits, but the findings underscore how the search continues for effective therapies to treat Alzheimer’s.
The drug, bumetanide, is commonly available and inexpensive and has been used for decades to treat the fluid buildup that accompanies heart failure, kidney disease, liver disease, and other ailments. Also known as a diuretic or “water pill,” the drug causes people to pee more, reducing fluid buildup. Diuretics are commonly prescribed to treat high blood pressure as well.
The study, which analyzed health records from millions of Americans, found that people who carried the APOE-E4 gene variation, which increases the risk of developing Alzheimer’s, were significantly less likely to develop the disease if they had been taking bumetanide, compared to their high-risk peers who weren’t taking the drug. The drug also appeared to reverse signs of Alzheimer’s disease in mouse and human cell experiments. The findings were published in the journal Nature Aging.
“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 Alzheimer’s disease,” said Dr. Richard J. Hodes, the director of the National Institute on Aging, part of the National Institutes of Health that helped fund the research.
For the study, researchers analyzed brain tissue from 213 men and women who carried the APOE-E4 gene allele and conducted a computational drug-repurposing screen. This means that they derived a sort of signature (gene expression profile) from the 213 people in the study. Then they compared those signatures to similar signatures obtained with more than 1,300 drugs that have been approved by the Food and Drug Administration. By cross-referencing the two types of signatures, they identified five drugs showing promise in helping to neutralize the effects that APOE-E4 had on the brain, with bumetadine showing the greatest potential benefits.
The researchers then confirmed their finding by performing experiments in the laboratory and found that treating mice which expressed the human APOE-E4 gene with the drug reduced learning and memory deficits. The neutralizing effects were also confirmed in human-derived cell experiments, which suggested that people already taking bumetanide should have lower rates of Alzheimer’s.
To further test this in real life, the research team analyzed the electronic health records from more than 5 million people and divided them into two groups: adults over 65 who took bumetanide, and a matching group who did not take the drug. The analysis showed that those who had a high genetic risk for Alzheimer’s and took bumetanide had a 35 to 75 percent lower prevalence of Alzheimer’s disease compared to those not taking the drug.
“We know that Alzheimer’s disease will likely require specific types of treatments, perhaps multiple therapies, including some that may target an individual’s unique genetic and disease characteristics — much like cancer treatments that are available today,” said Dr. Jean Yuan, Translational Bioinformatics and Drug Development program director in the NIA Division of Neuroscience. “ The next step, the researchers say, will be to test the drug directly in Alzheimer’s patients.
Many drugs show promise in early-stage trials, only to fail in late-stage studies involving thousands of participants. Finding new uses for old drugs is called repurposing, and it is one of many approaches to Alzheimer’s research.
But finding effective treatments is critical. Most current therapies show only limited benefits in curbing declines in memory and thinking skills, and no drugs have been shown to cure or prevent Alzheimer’s. The Fisher Center for Alzheimer’s Research Foundation continues to fund vital research into the underlying causes of Alzheimer’s, which may one day lead to more effective treatments.
By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.
Source: Alice Taubes, Phil Nova, et al: “Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4-related Alzheimer’s disease.” Nature Aging, October 11, 2021