Filana Therapeutics' Simufilam Shows Dose-Dependent Seizure Reduction in Tuberous Sclerosis Complex Mouse Model
Key Insights
Filana Therapeutics (search) published preclinical data in Epilepsia showing simufilam attenuated seizure progression in a dose-dependent manner in a severe TSC mouse model.
The study demonstrated a statistically significant correlation between simufilam dose and reduced seizure frequency over a three-week monitoring period.
TSC-related epilepsy (search) affects approximately 45,000 people in the U.S., with more than 60% of patients remaining refractory to current antiepileptic therapies.
Filana Therapeutics (search) announced the publication of preclinical data in Epilepsia demonstrating that simufilam, an oral small molecule designed to modulate filamin A (search) protein, attenuated seizure progression in a well-established mouse model of severe Tuberous Sclerosis Complex (search) (TSC)-related epilepsy. The study showed a dose-dependent reduction in seizure activity, providing additional scientific support for the drug's potential therapeutic application.
Study Design and Results
The dose escalation study evaluated simufilam's ability to slow seizure worsening in the Tsc1 (search) conditional knockout mouse (Tsc1-cKO), described as an exceptionally severe and progressive model of TSC-related epilepsy (search). Seizures (search) were monitored for approximately three weeks following onset, with the data revealing that simufilam attenuated the progression of seizure activity compared to vehicle control.
The research demonstrated a statistically significant correlation between simufilam dose and the number of seizures (search) by the end of the study period. According to the published data, simufilam attenuated the expected worsening of seizures over time in both number and total duration, with the attenuation of seizure worsening increasing with drug exposure.
The study was led by Angélique Bordey, PhD, Senior Vice President of Neuroscience at Filana Therapeutics (search) and Vice Chair of Research for the Department of Neurosurgery at Yale School of Medicine. The work was conducted in collaboration with the TSC Alliance (search) and PsychoGenics (search), Inc., the clinical research partner of the TSC Preclinical Consortium.
Clinical Significance and Unmet Need
TSC is a rare genetic disorder resulting from mutations in the TSC1 (search) or TSC2 (search) genes, affecting the mechanistic target of rapamycin (mTOR (search)) pathway and potentially causing tumors to grow in multiple organs. Epilepsy represents the most common health issue affecting the TSC community, with 80% to 90% of TSC patients experiencing seizures (search).
TSC-related epilepsy (search) affects approximately 45,000 people in the United States, with most patients beginning to experience seizures (search) within their first year of life. Despite multiple approved treatments currently available, more than 60% of TSC patients remain refractory to antiepileptic therapy, highlighting a significant unmet medical need.
Regulatory Status and Next Steps
Filana Therapeutics (search) is currently addressing a clinical hold placed by the FDA in December 2025. The company is working to provide additional preclinical data and protocol design modifications as requested by the regulatory agency. According to CEO Rick Barry, the company remains focused on generating the necessary data to resolve the clinical hold and advancing their program for the TSC community.
"The formal publication of these data in Epilepsia supports our previously reported findings and reinforces the biological rationale for studying simufilam in TSC-related epilepsy (search)," said Dr. Bordey. "Together with our findings in an earlier animal model, these results underscore the positive correlation between seizure outcomes and plasma exposure to simufilam and bolster the scientific basis of our clinical program."
Research Collaboration Framework
The study was conducted through the TSC Alliance (search) Preclinical Consortium, a collaborative partnership that unites academic and industry researchers to test potential therapies for TSC-related epilepsy (search). The consortium accelerates drug development by evaluating new and repurposed compounds in standardized animal models to move promising potential treatments into clinical trials more efficiently.
The Tsc1 (search)-cKO mouse model used in the study was developed by Michael Wong, MD, PhD, at Washington University School of Medicine and is housed at PsychoGenics (search), Inc., in collaboration with the TSC Alliance (search). PsychoGenics is a preclinical Contract Research Organization specializing in central nervous system and orphan diseases, with a focus on psychiatric and neurological conditions including seizure disorders.
The paper, titled "The small molecule simufilam dose-dependently attenuates the worsening of seizures (search) in a mouse model of tuberous sclerosis complex (search)," was published online in Epilepsia on April 14, 2026. The top-line results of the study were previously reported by the company in August 2025.