Researchers have discovered a potential treatment that could help people with post-traumatic stress disorder (PTSD) and those struggling with traumatic memories by reversing the brain’s inability to extinguish fear memories.

Known as KDS2010, the drug, already in human trials, targets a brain chemical imbalance by blocking an enzyme that triggers excess production of gamma-aminobutyric acid (GABA) in the brain.

Before now, PTSD treatment has largely relied on medications that target serotonin, such as selective serotonin reuptake inhibitors (SSRIs). These are based on research linking the disorder to reduced serotonin levels and changes in serotonin transporter activity. However, such drugs offer only limited relief for many patients, leaving a gap in effective treatment options.

Scientists at the Institute for Basic Science (IBS) and EwhaWomans University said PTSD may be driven by excessive GABA produced by astrocytes, star-shaped support cells in the brain. They explained that this surplus GABA disrupts the medial prefrontal cortex (mPFC), a region that regulates fear, making it difficult for patients to extinguish traumatic memories long after the threat has passed.

The team’s findings came from brain imaging studies of more than 380 people, which showed that PTSD patients had unusually high GABA levels and reduced blood flow in the mPFC. Patients who showed clinical improvement had lower GABA levels, indicating the chemical’s central role in recovery.

To trace the source of this imbalance, the researchers examined postmortem human brain tissue and PTSD-like mouse models. They found that astrocytes, not neurons, were producing abnormal amounts of GABA through the enzyme monoamine oxidase B (MAO-B). This astrocyte-derived GABA weakened neural activity and blocked the brain’s ability to forget fear.

The study revealed that KDS2010, a highly selective and reversible MAO B inhibitor developed at IBS, could reverse PTSD-like symptoms in mice. According to the researchers, the drug reduced GABA levels, restored blood flow in the mPFC, normalised brain activity, and enabled fear extinction. KDS2010 has passed Phase 1 safety trials in humans and is currently in Phase 2 trials.

Postdoctoral researcher and co-first author, Dr Won Woojin, said the study was the first to identify astrocyte-derived GABA as a driver of fear extinction deficits in PTSD. He noted that the results offered preclinical evidence for a new therapeutic approach using MAO-B inhibitors.

Study Director, Dr Justin Lee, described the research as a “reverse translational” process, starting with clinical brain scans in humans, identifying the cellular cause in the lab, and then confirming the mechanism in animal studies. He added that the findings could pave the way for new treatments not only for PTSD but also for panic disorder, depression, and schizophrenia.

The researchers noted that they plan to continue exploring astrocyte-targeted therapies for various neuropsychiatric disorders, expressing hope that KDS2010 could become a viable option for patients who do not respond to current serotonin-based treatments.