Ketamine is an anesthesia medicine that may be a powerful antidote to depression – if only scientists knew more about how it affects the brain. A group of researchers at Des Moines University and the University of North Carolina recently landed a grant from the National Institutes of Health (NIH) for their innovative proposal to try to answer that question.
“Ketamine’s antidepressant property stands out because it works very fast compared to commonly used antidepressant medications – in hours rather than weeks,” says neuroscience researcher LiLian Yuan, Ph.D., associate professor of physiology and pharmacology at DMU and the principal investigator on the grant. “But the scientific field doesn’t have a consensus on how ketamine works. That prevents the field from moving forward.”
First used during the 1960s, ketamine eases pain by helping sedatives work more effectively. When misused, however, it can impair a person’s sense of sight and sound and ability to speak and move. Abused as a date-rape drug, ketamine can cause a person to have hallucinogens or become unconscious.
At the same time, ketamine has the potential to help patients suffering from depression, which affects 16 percent of people worldwide. That motivates Yuan and her DMU collaborators, Eric Wauson, Ph.D., and Vanja Duric, Ph.D., assistant professor and associate professor, respectively, of physiology and pharmacology. Their co-investigator is Lee Graves, Ph.D., professor and director of graduate studies in the pharmacology department, University of North Carolina School of Medicine. The three DMU researchers first connected with Graves – who was Wauson’s Ph.D. adviser – two years ago after learning he’d developed a novel approach, kinome profiling, that may help them better understand ketamine’s fast-acting mechanism.
A kinome is a collection of the 518 protein kinases in the human genome. They act as key regulators of cell function. Graves’ approach, which uses methods of mass spectrometry, allows researchers to detect active protein kinases in the entire kinome, rather than one kinase at a time.
“We started using kinome profiling to study heart cells’ reaction to hypoxia,” says Wauson, who conducts research on cellular processes and particularly on heart disease.
Duric, whose research focuses on neural mechanisms and depression, adds that this new grant represents the first time kinome profiling has been used in neuroscience research and specifically on depression. That’s why it’s a “perfect fit” for the type of NIH funding, an R21 grant, the project received. Its title is “Identification of a Novel Antidepressant Mechanism of Ketamine by Kinome Profiling.”
“R21 grants are designed to fund exploratory research that’s cutting-edge and based on new techniques or approaches not tried before,” he says.
The researchers hope their work will reveal new information that could lead to new treatments for a debilitating disease and spur additional research.
“Once our data is available, we’ll make it accessible to peers in the field. We hope to promote additional collaborations,” Yuan says. “It also creates opportunities for our students to participate in cutting-edge research related to their future health care practice.”
