Could an Old Drug Be a New Alzheimers Treatment? – AARP

Posted: October 17, 2021 at 5:15 pm

Isolating a risk factor for Alzheimers disease

The federally funded research focused its analysis on a specific population: those with a genetic variant known as APOE4. While scientists dont fully understand what causes Alzheimers 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 persons risk for Alzheimers. While not everyone who carries APOE4 gets Alzheimers, 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 Alzheimers Association.

For the study, the team of researchers first examined changes that take place over time in brain tissue samples of people with APOE4. Then they combed through a database of nearly 1,300 federally approved drugs in search of candidates to potentially reverse such gene-related changes. Bumetanide, which was approved by the U.S. Food and Drug Administration (FDA) decades ago, emerged as the strongest contender.

When the research team gave bumetanide to mice that were engineered to have two copies of the human APOE4 gene, they found that the drug helped reduce deficits in learning and memory. The drugs counteracting effects were also seen in neurons derived from skin cells of Alzheimers patients carrying the APOE4 gene.

Data from thousands of health records gave the researchers even more confidence in bumetanides potential effect on Alzheimers 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 Alzheimers 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.

As theyre based on a specific at-risk population, the teams findings lend support to a treatment approach called precision medicine, which has grown increasingly popular inAlzheimers research. It veers from a one-size-fits-all model and considers individual differences in environment, lifestyle and genetics indrug development and treatment decisions.

The traditional drug development approach for Alzheimers 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.

Now, experts increasingly say the answer to ending Alzheimers probably doesnt lie in a single drug or therapy. Tackling the disease will likely require specific types of treatments, perhaps multiple therapies, including some that may target an individuals unique genetic and disease characteristics much like cancer treatments that are available today, Jean Yuan, M.D., a program director in the NIAs Division of Neuroscience, said in a statement.

A major reason: The disease cant be pinned to one cause, at least in most people. Experts say it's likely due to a combination of age-related changes in the brain, along with genetic, environmental andlifestyle factors.

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.

Theres 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 Alzheimers disease, and most just help to briefly manage symptoms of the illness, which afflicts more than 6 million Americans. Earlier this year, the agencygranted approvalto a drug the first of its kind that may slow the progression of the disease. However, the medication hasnt yet been proven to alter symptoms or outcomes of Alzheimers, such as the advancement of cognitive decline and dementia, according to the NIA.

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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Could an Old Drug Be a New Alzheimers Treatment? - AARP

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