Common Diuretic Emerges as Potential Precision Medicine Treatment for Alzheimer’s Disease

Hospitals someday may be able to treat certain types of Alzheimer’s by combining a precision medicine approach with an existing drug

Hospital leaders may be as intrigued as scientists were to learn that certain Alzheimer’s disease cases might be treatable using a common diuretic.

Researchers examining a database of individuals who had a specific genetic risk for Alzheimer’s disease found that those who took the diuretic bumetanide had a 35% to 75% lower risk of developing the illness than people using other diuretics. The National Institutes of Health (NIH) funded the study.

A team from the independent Gladstone Institutes studied more than 210 brain tissue samples.

Gladstone researchers also teamed up with scientists from the University of California San Francisco and Icahn School of Medicine at Mount Sinai in New York to analyze electronic health records of millions of patients. The researchers examined how a gene strongly connected with the development of Alzheimer’s disease was expressed. The unique signature of the gene, called APOE4, was then compared against a database of almost 1,300 U.S. Food and Drug Administration (FDA) approved medications.

The researchers found that bumetanide, a diuretic medication in use for more than 30 years to decrease fluid levels and treat heart failure, emerged as the most helpful option in changing the expression of the APOE4 gene.

In the study, recently published in Nature Aging, the Gladstone team tested its findings by examining the prevalence of Alzheimer’s disease in patients who have used bumetanide when compared to the rest of the population. They found that there was a meaningful reduction in Alzheimer’s rates when bumetanide was used. The team also validated its findings using mice and human neuron cells.

New Approach to Alzheimer’s Yields a Different Treatment Path

The bumetanide study is not a typical approach to studying Alzheimer’s drugs, nor is it common to look at treatments based on a certain Alzheimer’s patients.

“The traditional drug development approach for Alzheimer’s disease has been focusing on one protein, one gene, or one cellular pathway,” said study co-author Yadong Huang, MD, PhD, in a recent Gladstone Institutes statement. “The assumption for many years has been that we may find a magic bullet that will fit every Alzheimer’s disease patient.”

Huang is the director of the Center for Translational Advancement at Gladstone Institutes and a professor of neurology and pathology at the University of California San Francisco.

“If you look at Alzheimer’s disease patients on the surface, they all have dementia, but their underlying molecular or cellular mechanisms might not be exactly the same,” Huang continued. “Combining so-called precision medicine with drug repurposing and with real-world data analysis will help us dramatically speed up drug development targeting those aging-related complex diseases.”

New Precision Treatments Using Existing Drugs

This recent research illustrates the importance of precision medicine in not just developing new, genetic-specific medications, but also in researching new precision medicine applications for existing drugs.

“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 National Institutes on Aging Director Richard J. Hodes, MD, in an NIH statement.

While this initial research has shown a promising precision medicine application for an existing drug, further research will be needed before widespread clinical use can begin. “Our next step, of course, will [be to] move to the real clinical trial to test the efficacy of bumetanide directly in Alzheimer’s patients,” said Huang.

This new application of bumetanide offers a potential treatment for some patients with Alzheimer’s disease. The study also emphasizes the importance for hospital leaders to be aware of new precision medicine discoveries that repurpose existing treatments.

—Caleb Williams