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Could an Old Drug Be a New Alzheimer s Treatment

Researchers find potential in repurposing a common diuretic but say more studies are needed

Mladen Zivkovic / Getty Images The search for a drug that can stop or reverse the ravages of Alzheimer’s disease has been riddled with setbacks in recent years. But new research suggests a potential advance from an unexpected source: an already approved pill currently prescribed to treat fluid retention associated with heart failure, kidney disease and other common conditions.
In a published this week in the journal Nature Aging, the diuretic bumetanide was shown to reverse signs of Alzheimer’s in mice tha t carried a genetic risk factor for the disease, as well as in human brain cells in the lab. What’s more, an analysis of health records revealed that older adults who took bumetanide were less likely to develop Alzheimer’s disease than those on a different diuretic. Get instant access to members-only products and hundreds of discounts, a free second membership, and a subscription to AARP the Magazine. “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,” National Institutes on Aging (NIA) Director Richard J. Hodes, M.D., said in a statement.

Isolating a risk factor for Alzheimer s disease

The federally funded research focused its analysis on a specific population: those with a genetic variant known as APOE4. While scientists don’t fully understand what causes Alzheimer’s disease, they do know some people are more likely than others to develop it based on their genetic makeup. The APOE gene in particular is involved in making a protein that helps carry cholesterol and other types of fat in the bloodstream. It comes in at least three different variations, and one of them, called APOE4, increases a person’s risk for Alzheimer’s. While not everyone who carries APOE4 gets Alzheimer’s, an estimated 40 to 65 percent of those diagnosed with the disease have at least one copy of the gene variation (also called an allele), according to the Alzheimer’s Association. AARP Membership — $12 for your first year when you sign up for Automatic Renewal Get instant access to members-only products and hundreds of discounts, a free second membership, and a subscription to AARP the Magazine. Entertainment $3 off popcorn and soft drink combos See more Entertainment offers > Data from thousands of health records gave the researchers even “more confidence” in bumetanide’s potential effect on Alzheimer’s disease, says study coauthor Yadong Huang, M.D., director of the Center for Translational Advancement at Gladstone Institutes and a professor of neurology and pathology at the University of California, San Francisco. An analysis showed that adults 65 and older who took bumetanide were 35 to 75 percent less likely to be diagnosed with Alzheimer’s disease than those who took another diuretic. “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,” says Huang, who is hopeful that these trials could start as early as next year.

Why such precision medicine may matter

As they’re based on a specific at-risk population, the team’s findings lend support to a treatment approach called precision medicine , which has grown increasingly popular in . It veers from a one-size-fits-all model and considers individual differences in environment, lifestyle and genetics in . “The traditional drug development approach for Alzheimer’s disease has been focusing on one protein, one gene or one cellular pathway,” Huang says. “The assumption for many years has been that we may find a magic bullet that will fit every Alzheimer's disease patient.” AARP Membership — $12 for your first year when you sign up for Automatic Renewal Get instant access to members-only products and hundreds of discounts, a free second membership, and a subscription to AARP the Magazine. . “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 says. Breaking down the patient population into subgroups, such as genetic risk, could be a more effective way to study potential treatments, he argues. There’s also a plus to exploring new uses for old drugs that already have a proven track record for safety — a strategy known as drug repurposing. Finding one that works could cut years off the time it typically takes to get a treatment from clinical trials to patient use. “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,” Huang says. So far only a handful of drugs have been approved by the FDA for Alzheimer’s disease, and most just help to briefly manage symptoms of the illness , which afflicts more than 6 million Americans. Earlier this year, the agency to a drug — the first of its kind — that may slow the progression of the disease. However, the medication hasn’t yet been proven to alter symptoms or outcomes of Alzheimer’s, such as the advancement of cognitive decline and dementia, according to the NIA. What It's Like to Care for Someone With Dementia Rachel Nania writes about health care and health policy for AARP. Previously she was a reporter and editor for WTOP Radio in Washington, D.C. A recipient of a Gracie Award and a regional Edward R. Murrow Award, she also participated in a dementia fellowship with the National Press Foundation.
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