New Path for Treating Pediatric Epilepsy 'Dravet Syndrome' with Recurrent Seizures [Reading Science]

Discovery of Drug Candidate Modulating SCN1A Dysfunction by GIST and Korea Research Institute of Chemical Technology
Seizure Suppression Demonstrated in Animal Models

A new drug candidate that could increase the possibility of treating Dravet syndrome-a rare pediatric epilepsy that develops within the first year of life and causes recurrent convulsive seizures-has been developed by a domestic research team.

A joint research team led by Professor Jinhui Ahn of the Department of Chemistry at Gwangju Institute of Science and Technology (GIST), and Dr. Myungae Bae and Dr. Kiyoung Kim from the Korea Research Institute of Chemical Technology, announced the discovery of a small molecule drug candidate, "GM-91466," for the treatment of intractable pediatric epilepsy.

Blueprint for a New Dravet Syndrome Candidate Compound. A new chemical scaffold (1,3,4-oxadiazolone) candidate compound with superior efficacy compared to existing drugs has been developed. It acts strongly even in small amounts, selectively targets specific proteins, and can be synthesized in four steps using low-cost materials. Provided by the research team.

Dravet syndrome is a serious and rare neurological disorder that begins with seizures accompanied by high fever within the first year of life, followed by recurrent convulsions and developmental delays as the child grows. The main cause is known to be a dysfunction of the SCN1A gene, which regulates signal transmission in brain neurons. Most current treatments use drugs originally developed for other conditions, which often do not provide sufficient efficacy or may carry the risk of side effects.

Regulation of SCN1A gene dysfunction... Seizure suppression observed in animal models

The research team screened drug candidates using animal models that closely mimic the causative genetic abnormality of the disease.

First, in a zebrafish model engineered to replicate SCN1A gene dysfunction, a comparison of various compounds showed that GM-91466 strongly suppressed seizure-related abnormal behaviors while having no effect on the movement of normal individuals.

Subsequently, in a mouse model with partially reduced SCN1A function, the compound significantly decreased both the frequency and intensity of seizures and delayed the onset of seizures, demonstrating superior potential compared to existing drugs.

Research team photo. From left to right: Donggeon Kim, PhD candidate (co-first author, Department of Chemistry, GIST), Kyuseok Hwang, PhD (co-first author, Korea Research Institute of Chemical Technology), Kiyoung Kim, PhD (corresponding author, Korea Research Institute of Chemical Technology), Jinhui Ahn, Professor (corresponding author, Department of Chemistry, GIST). Courtesy of GIST

The research team also elucidated the mechanism of action of this candidate compound. GM-91466 was found to increase the expression of tryptophan hydroxylase (TPH2), an enzyme responsible for serotonin synthesis, thereby raising serotonin levels in the brain. Serotonin is a key neurotransmitter in maintaining the balance of signals between neurons and plays an essential role in stabilizing excessively excited neural circuits.

Whereas some existing drugs act by directly stimulating serotonin receptors, GM-91466 increases serotonin production itself, representing a new therapeutic approach.

Oral administration possible... Preclinical safety also confirmed

The research team further confirmed that this candidate compound is effectively delivered to the brain through the bloodstream after administration. Stable efficacy was observed even with oral administration, and preclinical safety evaluations, including assessments for cardiac toxicity, genotoxicity, and short-term repeated-dose toxicity, revealed no significant abnormalities.

Professor Jinhui Ahn explained, "GM-91466 is a novel small molecule candidate that modulates the hyperexcitability of neural circuits caused by SCN1A gene dysfunction-the fundamental cause of Dravet syndrome. By increasing the enzyme responsible for serotonin production and restoring neuronal signal balance, it has been shown to reduce seizures through a different mechanism than existing drugs."

She added, "This study presents a new strategy for the treatment of intractable pediatric epilepsy, and suggests the potential for expansion to various neurological disorders that arise from similar mechanisms beyond Dravet syndrome."

This research was supported by the Basic Research Program of the Ministry of Science and ICT and the National Research Foundation of Korea, as well as the Healthcare Technology R&D Project of the Ministry of Health and Welfare and the Korea Health Industry Development Institute. The results were published online in the Journal of Medicinal Chemistry, an international journal in the field of medicinal chemistry, on January 23, 2026.

This content was produced with the assistance of AI translation services.