Bumetanide diuretic pill shows potential as Alzheimer’s disease treatment

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The widely available bumetanide diuretic pill has emerged as a potentially effective medication for treating Alzheimer’s disease.

A novel study funded by the National Institute on Aging (NIA) has determined that bumetanide – a commonly used and potent oral diuretic pill – may provide an unexpected yet efficacious treatment for those at genetic risk of Alzheimer’s disease.

The research illuminated that people taking bumetanide, which is approved by the US Food and Drug Administration (FDA), had a significantly lower prevalence of Alzheimer’s disease than those not taking the drug.

Richard J. Hodes, the NIA Director, said: “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.”

The findings of this groundbreaking discovery, published in the journal Nature Aging, advance a precision medicine approach for people at a higher risk of developing Alzheimer’s due to their genetic makeup.

Genetic risk factors

The research team understood that one of the most prevalent genetic risk factors for late-onset Alzheimer’s disease is a type of apolipoprotein E gene named APOE4. To investigate how to mitigate the expression of APOE4, the scientists examined data obtained from 213 brain tissue samples, identifying the gene expression signatures of Alzheimer’s – the levels to which the genes are turned on or off specific to APOE4 carriers.

Subsequently, the team examined the APOE4-specific Alzheimer’s signatures against those of over 1,300 drugs approved by the FDA, of which five demonstrated a gene expression signature that had the potential to neutralise the disease. The most promising of the final candidates was bumetanide, a diuretic employed to remedy fluid retention incurred by medical problems such as kidney, heart, and liver disease.

Testing bumetanide

To further authenticate the potential of the drug signified by the data-driven testing, the team performed examinations of bumetanide on mouse models with Alzheimer’s and induced stem-cell-derived human neurons, finding that the diuretic reduced memory and learning deficits in mice expressing the human APOE4 gene. These results were further validated in the human cell-based models, indicating that there should be lower rates of Alzheimer’s in people who were already taking bumetanide.

To investigate this hypothesis, the researchers employed electronic health record data sets from over five million people, which were divided into two groups: those over the age of 65 who took the medication and a matching group who did not. The analysis showed that those who took bumetanide and had a genetic risk had between 35% and 75% lower prevalence of Alzheimer’s disease compared to those who did not take the medication.

Jean Yuan, the Translational Bioinformatics and Drug Development program director in the NIA Division of Neuroscience, said: “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. The data in this paper make a good case to conduct a proof-of-concept trial of bumetanide in people with genetic risk.”

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