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School of Medicine Columbia

Neuroscientists identify new therapeutic to aid in sleep quality for those with severe psychiatric illness

University of South Carolina School of Medicine Columbia researcher, Ana Pocivavsek, Ph.D., and her team of investigators have published a study that shows reducing kynurenic acid with the use of a KAT II inhibitor helped improve sleep quality and duration in a lab study on rodents. The findings, which were published in Translational Psychiatry, may prove to be extremely beneficial for those who suffer from sleep disturbances, especially individuals with severe psychiatric illness. 

Sleep problems are common for those who suffer from neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Individuals may have difficulty falling asleep and may wake up often in the night. Prior research shows that kynurenic acid is increased in the brains of those who suffer from these illnesses. Pocivavsek’s study focused on the use of a KAT II inhibitor, which can in turn aid with a more restful sleep period. 

“The drug that we’ve studied reduces the amount of kynurenic acid, which is a product of tryptophan breakdown in the body,” Pocivavsek says. “We also know that individuals with severe psychiatric illness have increased tryptophan breakdown and increased kynurenic acid in their brains, so this drug is exciting to us because it will reduce this metabolism and have beneficial impacts on sleep.”

This drug would aid with sleep quality, which would in turn likely provide positive effects on the individuals’ daily life.  

“Improving sleep quality has a number of health benefits and this could improve everyday life for patients by reducing daytime sleepiness and improving daily function,” Pocivavsek added.   

Pocivavsek’s research shows exciting results surrounding the use of the KAT II inhibitor prior to sleep, and she hopes the published study can bring attention to more research on the topic. It may also be beneficial for those who don’t suffer from a psychiatric illness but do have issues with sleep quality.

“The findings in our present manuscript demonstrate that a kynurenine aminotransferase II (KAT II) inhibitor improves sleep outcomes in our disease model and also the experimental controls,” she says. “This is exciting to us because it demonstrates that reducing kynurenic acid prior to the onset of sleep has beneficial outcomes on sleep duration and quality. We hope this brings much needed attention to drug discovery research aimed at reducing kynurenic acid and balancing tryptophan metabolism to a healthy state, and in turn benefiting those who suffer sleep issues.”

Bolstered by their findings, Pocivavsek and her team have future studies planned.

“Our present study evaluated an acute, single dose of the KAT II inhibitor on sleep. Future studies will evaluate how beneficial the drug is when it is taken daily for an extended period. In addition, our future studies are also evaluating if the KAT II inhibitor can promote good quality sleep when the body is homeostatically challenged with sleep deprivation.”

Snezana Milosavljevic, Ph.D., a postdoctoral fellow in the School of Medicine Columbia Department of Pharmacology, Physiology and Neuroscience, is the first author of the manuscript. Pocivavsek’s team collaborated with Homayoun Valafar, Ph.D., professor and chair in the Department of Computer Science and Engineering, to expand on machine learning approaches to classifying sleep states. Andrew Smith and Courtney Wright also contributed to the study.

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