Using 4‑phenylbutyrate to help GAT‑1 proteins work in genetic epilepsy

Promoting Protein Trafficking with 4-phenylbutyrate to Treat Genetic Epilepsy

NIH-funded research Vanderbilt University Medical Center · NIH-11290424

This work uses the drug 4‑phenylbutyrate to help restore GAT‑1 protein function with the goal of reducing seizures and developmental problems in children with SLC6A1-related epilepsy.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionVanderbilt University Medical Center NIH-funded
Lab location1 site (Nashville, United States)
Project IDNIH-11290424 on NIH RePORTER

What this research studies

Researchers are studying how 4‑phenylbutyrate (PBA) can repair misfolded GAT‑1 proteins so they reach the cell surface and work properly. They will use patient-derived cell lines, a library of SLC6A1 mutations, and knockin mouse models to see how PBA changes protein trafficking and neuronal and astrocyte function. The team will integrate these lab findings with data from a promising pilot trial to identify which mutations respond and why. Results are intended to guide whether PBA could be used more broadly for children with SLC6A1-related epilepsy.

Who could benefit from this research

Good fit: Children (typically up to about 11 years old) with confirmed SLC6A1/GAT‑1 mutations who have seizures and/or developmental differences such as autism or intellectual disability are the most likely candidates.

Not a fit: People with epilepsy caused by other genes or mechanisms, or without SLC6A1/GAT‑1 mutations, are unlikely to benefit from this PBA-focused approach.

Why it matters

Potential benefit: If successful, this approach could improve seizure control and cognitive or behavioral outcomes in children with SLC6A1/GAT‑1 mutations by restoring normal protein activity.

How similar studies have performed: Early preclinical work and a small pilot trial show promising rescue of GAT‑1 function with PBA, but larger controlled studies are still needed to confirm clinical benefit.

Where this research is happening

Nashville, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.