New Alzheimer’s Treatment Advances Precision Medicine

In a study by the National Institute on Aging (NIA), researchers have found that a commonly available oral diuretic pill approved by the United States Food and Drug Administration is a potential treatment option for those at genetic risk of Alzheimer’s disease, advancing precision medicine.

The research indicates that those who took bumetanide had a significantly lower prevalence of Alzheimer’s disease compared to those who did not take the drug. The researchers analyzed information from databases of brain tissue samples and FDA-approved drugs. The team then examined human population studies to identify bumetanide as a leading potential drug treatment for Alzheimer’s.

“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,” NIA Director Richard J. Hodes, MD, said in a press release.

According to researchers, one of the most significant genetic risk factors of late-onset Alzheimer’s is a form of the apolipoprotein E gene called APOE4. Researchers analyzed data from 213 brain tissue samples, identifying the Alzheimer’s gene expression signatures specific to APOE4 carriers.

The team then compared the APOE4-specific Alzheimer’s signatures to more than 1,300 known FDA-approved drugs. Five drugs emerged with a gene expression signature that researchers thought could help neutralize the disease.

The strongest candidate was bumetanide, also used to treat fluid retention often caused by medical problems including heart, kidney, and liver disease. The researchers validated the data-drive findings by testing bumetanide in both mouse models of Alzheimer’s and induced pluripotent stem cell-derived human neurons.

Researchers discovered that treating mice expressing 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 the drug are at a lower risk of disease development.

To test the theory, 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 those who did not. The analysis indicated that those who had the genetic risk and took bumetanide had a 35 to 75 percent lower prevalence of Alzheimer’s disease than 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 Jean Yuan, MD, PhD, 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 discovery of bumetanide as a potential treatment for Alzheimer’s disease could not only improve chronic disease management with the widely accessible drug but also advance precision medicine practices.