7 days ago
PTSD Drug Discovery May Help Patients Let Go of Trauma
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A promising new drug could help people living with post-traumatic stress disorder (PTSD) finally let go of trauma.
This is the discovery of scientists at the Institute of Basic Science (IBS) and Ewha Womans University in South Korea who have identified a new brain mechanism driving the mental health condition—and a drug with the potential to counteract its effects.
The team has shown for the first time that "excessive" gamma-aminobutyric acid (GABA)—the brain's primary neurotransmitter—produced by star-shaped support cells in the brain known as "astrocytes" impairs the brain's ability to extinguish fear memories.
This inability to forget traumatic memories even after a long period of time is distinct to PTSD and has posed a major hurdle for treatment. Current medications targeting serotonin receptors offer limited relief for only a subset of patients, the authors said.
"Current FDA-approved treatments for PTSD are mainly SSRIs, which focus on reducing general symptoms like anxiety and mood instability," study author Dr. Woojin Won told Newsweek.
"However, only about 20–30 percent of patients achieve full remission, which is often unsatisfactory. Our approach is fundamentally different."
Woman with head in hands in dark room.
Woman with head in hands in dark room.
Domepitipat/Getty Images
Won continued: "While prefrontal cortex (PFC) dysfunction has been consistently reported in PTSD, the role of GABAergic mechanisms in this dysfunction has not been fully explored."
The researchers found that a brain-permeable drug called KDS2010, which selectively blocks an enzyme called 'monoamine oxidase B' (MAOB) responsible for this abnormal GABA production, can reverse PTSD-like symptoms in mice.
"It targets the pathological reactive astrocyte-derived GABA at the source," said Won.
"Unlike traditional MAO inhibitors, which can have off-target effects and are irreversible, KDS2010 is highly selective, reversible, and brain-penetrant, making it safer and more targeted."
They report the drug has already passed Phase 1 safety trials in humans, which makes it a "strong candidate" for future PTSD treatments.
GABA can be a positive thing, helping to regulate motor function, sensory processing and emotional stability. It can also offer calming effects, including helping to reduce anxiety and stress by controlling overactive neurons.
"However," Won explained, "GABA does not act uniformly across the brain, and its outcome varies depending on the target circuit.
"While GABA is generally calming, in this context [of the researcher's findings], it was silencing a circuit that the brain needs to overcome fear. This highlights that the effect of GABA is not simply good or bad, but it critically depends on where it acts and what neural circuits are involved."
Digital illustration showing brain waves and activity.
Digital illustration showing brain waves and activity.
selvanegra/Getty Images
The study focused on the medial prefrontal cortex (mPFC), a region of the brain critical for regulating fear. It found that PTSD patients had unusually high levels of GABA and reduced cerebral blood flow in this area, based on brain imaging studies of more than 380 participants.
On the other hand, GABA levels decreased in patients who showed clinical improvement, suggesting the chemical has a central role in recovery.
To unearth the origin of the excess GABA, the researchers examined postmortem human brain tissue and used PTSD-like mouse models. They discovered that astrocytes, not neurons, were producing abnormal amounts of GABA via the MAOB enzyme. This astrocyte-derived GABA impaired neural activity, blocking the brain's ability to forget traumatic memories.
"This inspired us to investigate astrocytic GABA dysregulation as a potential driver of PTSD pathology, and ultimately, as a novel therapeutic target," said Won.
Explaining further how "excessive" GABA in PTSD is produced, he added: "Trauma and stress might increase putrescine metabolism, which raises the levels of MAOB's presubstrate, leading to more GABA production.
"At the same time, the enzyme that breaks down GABA, ABAT, is reduced. Together, this combination causes the accumulation of astrocytic GABA and excessive tonic inhibition in key brain regions like the PFC."
When the team administered KDS2010, "a highly selective, reversible MAOB inhibitor" developed at IBS, the mice showed normalized brain activity and were able to extinguish fear responses.
The promising drug reduced GABA levels, restored blood flow in the mPFC, and re-enabled memory extinction mechanisms. This confirms astrocytic MAOB as a central driver of PTSD symptoms and MAOB inhibition as a viable therapeutic path.
The researchers flagged a major challenge of the study was linking clinical findings in humans with cellular mechanisms in the lab. They addressed this by applying a "reverse translational" strategy, beginning with clinical brain scans and moving backward to identify the cellular source of dysfunction. They then confirmed the mechanism and tested drug effects in animal models.
This led to a new understanding of how glial cells—non-neuronal cells long thought to be passive—actively shape psychiatric symptoms.
Would this type of drug be used alongside other methods like talking therapy for PTSD? "DS2010 alone has a strong potential to restore brain function by normalizing astrocytic GABA and improving fear extinction. However, we think that combining it with psychotherapy, especially exposure-based therapy, could create even greater synergy. By reducing abnormal inhibition in fear extinction circuits, KDS2010 may help the brain become more responsive to therapeutic input," Won explained.
How would it be administered? "KDS2010 is an orally available small molecule. In preclinical and early-phase clinical studies, it has been administered once daily in capsule or liquid form. This makes it highly feasible for long-term outpatient use, similar to antidepressants."
What about side effects? "In the Phase 1 clinical trial, KDS2010 was found to be well tolerated, with no serious adverse effects reported, even at higher doses. This safety is largely due to its selectivity for MAOB and its reversible mechanism, which avoids the long-term enzyme compensation seen with older MAO inhibitors. Nevertheless, larger trials in PTSD patients will be needed to fully assess tolerability and any rare side effects."
Won said the drug is currently undergoing Phase 2 trials for other neurological disorders, which means its safety profile is already being tested extensively in patients.
"Because of this, we believe it could reach the public faster than many other new drugs. If future trials for PTSD are successful and regulatory steps proceed smoothly, it could become available within a few years. Importantly, KDS2010 is part of a broader platform that may also be useful for treating other disorders involving astrocytic dysfunction, such as Parkinson's and Alzheimer's disease."
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Reference
Yoon, S., Won, W., Lee, S., Han, K., Ha, E., Lee, J., Hyeon, S. J., Joo, Y., Hong, H., Lee, H., Song, Y., Park, K. D., Huber, B. R., Lee, J., Edden, R. A. E., Suh, M., Ryu, H., Lee, C. J., & Lyoo, I. K. (2025). Astrocytic gamma-aminobutyric acid dysregulation as a therapeutic target for posttraumatic stress disorder. Signal Transduction and Targeted Therapy, 10(1), 240.
