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ETSU researchers obtain federal funding to discover new ways to fight depression

Brandon Paykamian • Aug 22, 2018 at 11:31 PM

With suicide claiming more than 1,000 lives per year in Tennessee and 40,000-plus annually in the United States, researchers are continually looking for new ways to treat major depression.

An East Tennessee State University team is looking into using existing cancer drugs — medicines that have already been approved for human use — for that treatment.

Dr. Greg Ordway, a professor in the ETSU Quillen College of Medicine, has studied the biology of depressive disorders for about three decades, and recently garnered federal funding to continue researching ways to treat depression, according to a Tuesday news release from the university.

“Current available antidepressants produce remission in only two-thirds of patients with depression, which affects over 15 million people in the United States each year,” Ordway said. “Our research is designed to unearth depression-related vulnerabilities of specific brain cells in hopes of uncovering novel targets for drugs that could better treat depression.”

The lead researcher and his team of colleagues discovered the possibility of a new way to treat depression after finding high levels of a particular enzyme in the brains of people who have died with major depression.

Ordway said researchers found that blocking PARP-1 enzymes with cancer drugs already on the market has an antidepressant effect. While PARP-1 enzyme inhibitors are often currently used alongside other cancer treatment drugs to make chemotherapy more effective, this enzyme is not targeted by current antidepressant drugs.

“When you treat cancer in someone with a DNA-damaging drug, the cancer cells increase PARP-1 to try to compensate for the damage, sort of like drug resistance,” he said. “We started looking at these enzymes that are used to repair damage and we found more of them (in people with depression).”

The National Institutes of Health recently awarded Ordway a two-year grant of more than $430,000 to continue his team’s research.

“After we were able to demonstrate an antidepressant effect (by inhibiting that enzyme) in an animal model, they got more interested in funding the research,” he said.

Ordway said this discovery could likely provide relief for millions around the world who are unresponsive to current antidepressants by repurposing drugs that already exist for other uses.

“These inhibitor drugs have already been tested in humans, so it’s more of a repurposing of the drug that’s used for cancer,” he said. “In theory, somebody could start using this really soon because the drugs are already approved for human use.

“They’re looking at drugs that are more toxic. We’re looking at drugs that aren’t as toxic like that; we’re looking for those that just inhibit the enzyme enough to produce an antidepressant effect.”

Those working alongside Ordway on the research project include Drs. Michelle Chandley, John Kalbfleisch and Yue Zou, as well as Dr. Craig Stockmeier from the University of Mississippi Medical Center and James Overholser from Case Western Reserve University.

In October, Ordway and Quillen colleague Dr. Russ Brown will receive additional funding from the American Foundation for Suicide Prevention for the development of a drug that treats depression through this new pathway.

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