Extreme ranges of GABA launched by astrocytes impair the mind’s capability to extinguish worry responses in PTSD, however a newly recognized drug goal presents promising hope for therapy.
Many individuals with post-traumatic stress dysfunction (PTSD) proceed to relive painful reminiscences lengthy after the precise risk is gone. Their brains appear unable to let go of worry, a phenomenon that has lengthy puzzled scientists and made efficient therapy tough. Present medicines that concentrate on serotonin receptors usually present solely restricted aid, and often assist only a fraction of these affected.
Now, researchers from the Institute for Fundamental Science (IBS) and Ewha Womans College have recognized a beforehand unknown mind course of which may be chargeable for this persistent worry response. They’ve additionally discovered a possible therapy that might change how PTSD is managed.
The examine, led by Dr. C. Justin LEE from the IBS Heart for Cognition and Sociality and Professor LYOO In Kyoon from Ewha Womans College, found that astrocytes (star-shaped help cells within the mind) can produce an excessive amount of GABA (gamma-aminobutyric acid). This extra GABA interferes with the mind’s capability to suppress fear-related reminiscences, a key problem for folks with PTSD.
Importantly, the staff examined a drug referred to as KDS2010 that crosses the blood-brain barrier and particularly blocks the monoamine oxidase B enzyme, which drives this irregular GABA manufacturing. In mouse fashions, the drug was in a position to cut back PTSD-like signs. KDS2010 has already accomplished Section 1 human security trials, positioning it as a promising possibility for future PTSD therapy.
Excessive GABA Ranges and Decreased Mind Exercise
PTSD stays tough to deal with, with present medicines concentrating on serotonin pathways offering restricted aid for a lot of sufferers. The brand new examine centered on the medial prefrontal cortex (mPFC), a area of the mind essential for regulating worry, and located that PTSD sufferers had unusually excessive ranges of GABA and decreased cerebral blood move on this space. These findings emerged from mind imaging research of greater than 380 contributors. Importantly, GABA ranges decreased in sufferers who confirmed medical enchancment, pointing to the chemical’s central function in restoration.
To uncover the origin of this extra GABA, the researchers examined postmortem human mind tissue and used PTSD-like mouse fashions. They found that astrocytes, not neurons, had been producing irregular quantities of GABA through the enzyme monoamine oxidase B (MAOB). This astrocyte-derived GABA impaired neural exercise, blocking the mind’s capability to overlook traumatic reminiscences.
When the researchers administered KDS2010, a extremely selective, reversible MAOB inhibitor developed at IBS, the mice confirmed normalized mind exercise and had been in a position to extinguish worry responses. The drug decreased GABA ranges, restored blood move within the mPFC, and re-enabled reminiscence extinction mechanisms. The examine thus confirms astrocytic MAOB as a central driver of PTSD signs, and MAOB inhibition as a viable therapeutic path.
A Reverse Translational Method
A significant problem of the examine was linking medical findings in people with mobile mechanisms within the lab. The researchers addressed this by making use of a “reverse translational” technique: they started with medical mind scans and moved backward to determine the mobile supply of dysfunction, then confirmed the mechanism and examined drug results in animal fashions. This strategy led to a brand new understanding of how glial cells — lengthy regarded as passive — actively form psychiatric signs.
“This examine is the primary to determine astrocyte-derived GABA as a key pathological driver of worry extinction deficit in PTSD,” mentioned Dr. WON Woojin, a postdoctoral researcher and co-first creator of the examine. “Our findings not solely uncover a novel astrocyte-based mechanism underlying PTSD, but additionally present preclinical proof for a brand new therapeutic strategy utilizing an MAOB inhibitor.”
Director C. Justin LEE, who led the examine, emphasised that “This work represents a profitable instance of reverse translational analysis, the place medical findings in human guided the invention of underlying mechanisms in animal fashions. By figuring out astrocytic GABA as a pathological driver in PTSD and concentrating on it through MAOB inhibition, the examine opens a very new therapeutic paradigm not just for PTSD but additionally for different neuropsychiatric problems corresponding to panic dysfunction, despair, and schizophrenia.”
The researchers plan to additional examine astrocyte-targeted therapies for varied neuropsychiatric problems. With KDS2010 at the moment present process Section 2 medical trials, this discovery might quickly result in new choices for sufferers whose signs haven’t responded to standard remedies.
Reference: “Astrocytic gamma-aminobutyric acid dysregulation as a therapeutic goal for posttraumatic stress dysfunction” by Sujung Yoon, Woojin Gained, Suji Lee, Kayoung Han, Eunji Ha, Juheon Lee, Seung Jae Hyeon, Yoonji Joo, Haejin Hong, Hyangwon Lee, Yumi Music, Ki Duk Park, Bertrand R. Huber, Junghee Lee, Richard A. E. Edden, Minah Suh, Hoon Ryu, C. Justin Lee and In Kyoon Lyoo, 28 July 2025, Sign Transduction and Focused Remedy.
DOI: 10.1038/s41392-025-02317-5
Funding: Institute for Fundamental Science
