A new study found that simufilam, an experimental oral drug, reduced seizure progression in a mouse model of tuberous sclerosis complex (TSC). Mice treated with medium and high doses of simufilam experienced fewer seizures and spent less time in seizures compared with untreated mice, whose seizures steadily worsened over time. The findings suggest simufilam could represent a promising new approach for treating severe epilepsy in people with TSC and support further testing in future clinical trials.
People with tuberous sclerosis complex (TSC) often have frequent and hard‑to‑control seizures. TSC is a genetic condition that affects brain development and many other parts of the body. In the brain, it can cause abnormal clusters of cells that make seizures more likely. Even with today’s medicines, many people with TSC continue to have seizures, so new treatments are badly needed.
This study looked at a drug called simufilam, a small molecule that is taken by mouth. Simufilam does not work the same way as most seizure drugs. Instead of calming brain cells directly, it is thought to act on a protein called filamin A, which helps shape brain cells and connect them to each other. Earlier studies suggested simufilam could reduce seizures in a mouse model of a related brain disorder. The researchers wanted to know if it could also help in TSC.
To test this, the scientists used a mouse model of TSC. These mice have a genetic change that causes brain abnormalities and seizures similar to those seen in people with TSC. Starting around the time of seizure onset, mice were treated twice a day with either simufilam or a placebo solution. Three doses of simufilam were tested.
The researchers recorded brain activity using continuous EEG. They tracked how many seizures each mouse had and how long the seizures lasted over several weeks.
The results were clear. Mice that did not receive simufilam showed a steady worsening of seizures over time. Mice that received a low dose of simufilam behaved much the same. However, mice given medium or high doses had a different outcome. In these mice, seizures did not get worse, even though this TSC model normally shows rapid seizure progression. Some mice on the highest dose had very few seizures near the end of the study.
The study also showed a dose‑response effect. Higher doses of simufilam led to fewer seizures and less total time spent in seizures. Blood tests showed that mice with higher levels of simufilam in their system generally had better seizure control.
Importantly, simufilam appeared to be well-tolerated in the TSC model as it did not impact animal weight.
The researchers also confirmed that filamin A levels were abnormally high in the brains of TSC mice, supporting the idea that this protein plays a role in the disease. Although simufilam did not lower filamin A levels directly, it may work by changing how this protein functions inside brain cells.
In summary, this study shows that simufilam can prevent seizures from getting worse in a mouse model of TSC, especially at higher doses. These results suggest simufilam could become a new type of seizure treatment for people with TSC. More studies are needed, but this work strongly supports testing simufilam further in clinical trials for epilepsy in TSC patients. A pharmaceutical company, Filana Therapeutics, hopes to start a clinical trial of simufilam in TSC in late 2026.
Lead author: Angelique Bordey, PhD, Senior Vice President, Neuroscience, Filana Therapeutics; and Rothberg Professor of Neurosurgery and Vice Chair of Research, Neurosurgery, Yale School of Medicine
Email address: abordey@filanatx.com
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