New drugs that target the GABAA α5 receptor to improve memory and thinking in schizophrenia
Official title: A preclinical therapeutic platform to develop GABAA alpha5 receptor positive allosteric modulators to improve cognitive function in schizophrenia
Funded at Johns Hopkins University · NIH-11145807 · Data updated 2026-11-12
Developing compounds that boost a specific brain receptor (GABAA α5) to help people with schizophrenia improve memory and other thinking skills.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Johns Hopkins University NIH-funded |
| Lab location | 1 site (Baltimore, United States) |
| Project start | August 1, 2024 |
| Project end | July 31, 2026 |
| Funding year | 2025 |
| Award (this year) | $204,688 |
| NIH project number | 5R21MH136532-02 |
| Project ID | NIH-11145807 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with schizophrenia who have noticeable memory or thinking difficulties, particularly those thought to involve hippocampal overactivity, would be the most likely candidates for future trials stemming from this work.
✕Less likely to help
People whose cognitive problems are caused primarily by medication side effects, other psychiatric or neurological disorders, or unrelated medical conditions may not benefit from this approach.
What this research studies
This project works in the lab to create and test drug-like molecules that positively modulate the GABAA α5 receptor, a protein common in the hippocampus that helps control brain excitation. Researchers will use cell-based tests and animal models to measure how selectively these compounds act on the α5 subunit and whether they restore the balance between excitation and inhibition in hippocampal circuits. The team will evaluate potency, selectivity, and effects on memory-related behaviors in preclinical models and optimize lead candidates for possible future clinical testing. At this stage the work is preclinical and does not involve giving these drugs to people, but it focuses on a mechanism tied to cognitive problems in schizophrenia.
Why it matters
Potential benefit: If successful, these drugs could improve memory and other cognitive abilities that current schizophrenia treatments do not effectively treat.
How similar studies have gone: Preclinical animal and cellular studies of GABAA α5 modulation have shown promise for improving memory by restoring inhibitory signaling, but human clinical evidence remains limited.
Where this research is happening
-
Johns Hopkins University
Baltimore, United States Active
Researchers
- Principal investigator: Koh, Ming Teng — Johns Hopkins University
- Study coordinator: Koh, Ming Teng
Related research
Other NIH-funded projects on the same topics.
-
Psychedelic-assisted approaches to help social and thinking skills in schizophrenia (preclinical and early-stage work)
This grant explores whether psychedelic-inspired compounds could help improve social skills and thinking flexibility in models related to schizophrenia, with a focus on how these effects might work alongside antipsychotic medications.
-
Using psychedelics to enhance social and cognitive abilities in schizophrenia
This study is looking at how certain psychedelics, like psilocybin and MDMA, might help improve social skills and thinking in people with schizophrenia, especially when used with regular medications, to find better ways to support those facing challenges with these symptoms.
-
Developing new treatments to enhance cognitive function in schizophrenia
This study is exploring new ways to help improve thinking and memory for people with schizophrenia by focusing on a specific brain receptor, hoping to find treatments that can make a real difference in their daily lives.
-
How specific anti-NMDAR1 antibodies in the blood may affect memory and brain protection
This research is exploring whether natural or abnormal anti-NMDAR1 antibodies in the blood influence memory, behavior, and brain protection in humans.
-
Understanding social disconnection in schizophrenia using digital signals and brain data
This grant explores how smartphones, social networks, and brain imaging can reveal why Veterans with schizophrenia have trouble forming and maintaining relationships, with the goal of guiding better treatments.
-
Understanding how autism and schizophrenia risk genes affect brain development
Scientists are testing how mutations in certain autism and schizophrenia risk genes change brain cells and networks, using patient-derived cells and organoids.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.