Researchers at the Institute for Basic Science (IBS) and Ewha Womans University have uncovered a new brain mechanism driving PTSD and identified a promising treatment. The team, led by Dr. C. Justin Lee at the IBS Center for Cognition and Sociality and Professor In Kyoon Lyoo at Ewha Womans University, found that excessive GABA (gamma-aminobutyric acid) produced by astrocytes—star-shaped support cells in the brain—impairs the brain’s ability to extinguish fear memories. This deficit is a core feature of PTSD that helps explain why traumatic memories persist long after danger has passed.
The Brain Mechanism Discovery
The study focused on the medial prefrontal cortex (mPFC), a region critical for regulating fear, and examined brain imaging studies of more than 380 participants. PTSD patients showed unusually high levels of GABA and reduced cerebral blood flow in this area. Examining postmortem human brain tissue and PTSD-like mouse models revealed that astrocytes—not neurons—produce abnormal amounts of GABA via the enzyme monoamine oxidase B (MAOB). This astrocyte-derived GABA impaired neural activity and blocked the brain’s ability to forget traumatic memories. Notably, GABA levels decreased in patients who showed clinical improvement.
The Drug Candidate
A drug called KDS2010, a highly selective and reversible MAOB inhibitor developed at IBS, reversed PTSD-like symptoms in mice. When administered, the drug normalized brain activity, restored blood flow in the mPFC, reduced GABA levels, and re-enabled memory extinction mechanisms. KDS2010 has already passed Phase 1 safety trials in humans and is currently undergoing Phase 2 clinical trials. Current PTSD medications targeting serotonin pathways provide limited relief for many patients, making this discovery significant.
Research Approach and Future Applications
The researchers employed a “reverse translational” strategy: beginning with clinical brain scans and moving backward to identify cellular sources of dysfunction, then confirming the mechanism in animal models. Director C. Justin Lee emphasized that this approach opens “a completely new therapeutic paradigm not only for PTSD but also for other neuropsychiatric disorders such as panic disorder, depression, and schizophrenia.”
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.sciencedaily.com/releases/2025/08/250803011817.htm