Clearing out “aged” brain cells dramatically reduced seizures and restored memory in a new epilepsy study.
Temporal lobe epilepsy is a neurological condition marked by repeated seizures and problems with memory and thinking. New research suggests it may also cause certain brain cells to age faster than normal. In a study led by scientists at Georgetown University Medical Center, researchers found that removing these prematurely aging cells in mice significantly reduced seizures, improved memory, and even prevented epilepsy from developing in some animals. The aging cells were eliminated using either genetic techniques or drug-based treatments.
The study was funded by the National Institutes of Health (NIH) and was published today (December 22) in the journal Annals of Neurology.
A New Treatment Strategy for Drug-Resistant Epilepsy
“A third of individuals living with epilepsy don’t achieve freedom from seizures with current medications.” says senior author Patrick A. Forcelli, Ph.D., professor and chair of Georgetown School of Medicine’s Department of Pharmacology & Physiology and the Jerome H. Fleisch & Marlene L. Cohen Endowed Professor of Pharmacology. “Our hope is that senotherapy, which involves using medications to remove senescent, or aging cells, could potentially minimize the need for surgery and/or improve outcomes after surgery.”
Temporal lobe epilepsy (TLE) can develop for many reasons. These include brain injuries caused by trauma or stroke, infections such as meningitis, brain tumors, abnormal blood vessel formations, and certain genetic conditions. TLE is the most common form of epilepsy that does not respond well to medication and affects roughly 40% of people with epilepsy.
Aging Support Cells Found in Human Epileptic Brain Tissue
To better understand the disease, the research team analyzed donated human brain tissue that had been surgically removed from the temporal lobes of patients with epilepsy. When compared with brain tissue collected during autopsies from individuals without epilepsy, the samples from TLE patients contained five times more senescent glial cells. Glial cells play a critical role in supporting and protecting neurons, although they do not generate electrical signals themselves.
Mouse Studies Show Reduced Seizures and Memory Improvement
The findings from human tissue led the researchers to examine whether the same buildup of aging cells occurred in mice engineered to develop TLE. Within two weeks of the brain injury that triggered epilepsy in the animals, the team observed clear increases in markers of cellular aging at both the gene and protein levels.
When treatments were used to eliminate these aging cells, the results were striking. Senescent cells were reduced by about 50%. The mice showed improved performance in maze-based memory tests, experienced fewer seizures, and about one-third of them were protected from developing epilepsy entirely.
Repurposed Drugs With Known Safety Profiles
The drug treatment tested in the mice combined dasatinib and quercetin. Dasatinib is a targeted therapy currently used to treat leukemia. Quercetin is a plant flavonoid found in fruits, vegetables, tea, and wine that can act as a powerful antioxidant and have anti-inflammatory properties. Together, the two drugs have been widely used in animal studies to eliminate senescent cells in a variety of disease models.
The researchers selected this combination in part because both drugs are already being tested in early phase clinical trials for other conditions. Forcelli also points out that dasatinib is FDA approved for a form of leukemia, meaning its safety profile is already well understood. This could help speed the path toward future clinical trials in people with epilepsy.
Links to Aging and Neurodegenerative Disease
The study’s first co-authors Tahiyana Khan, Ph.D. and David J. McFall, both trainees in Forcelli’s lab, note that aging of glial cells has also been linked to normal aging and to neurodegenerative disorders such as Alzheimer’s disease. This is another area the research team continues to investigate.
“We have ongoing studies using other repurposed drugs that can impact senescence as well as studies in other rodent models of epilepsy. We would like to understand the critical windows for intervention in epilepsy, and the hope is that these studies will lead to clinically useful treatments,” says Forcelli.
Reference: “Senescent Cell Clearance Ameliorates Temporal Lobe Epilepsy and Associated Spatial Memory Deficits in Mice” by Tahiyana Khan, David J. McFall, Abbas I. Hussain, Logan A. Frayser, Timothy P. Casilli, Meaghan C. Steck, Irene Sanchez-Brualla, Noah M. Kuehn, Michelle Cho, Jacqueline A. Barnes, Brent T. Harris, Stefano Vicini and Patrick A. Forcelli, 22 December 2025, Annals of Neurology.
DOI: 10.1002/ana.78118
In addition to Forcelli, Khan and McFall, authors at Georgetown include Abbas I. Hussain, Logan A. Frayser, Timothy P. Casilli, Meaghan C. Steck, Irene Sanchez-Brualla, Ph.D., Noah M. Kuehn, Michelle Cho, Jacqueline A. Barnes, M.D., Brent T. Harris, M.D., Ph.D., and Stefano Vicini, Ph.D.
Forcelli and his co-authors report having no personal financial interests related to the study.
This work was supported by NIH grants R21NS125552, F99NS129108, T32NS041218, T32GM142520, F30NS143374-01, T32GM144880 and T3GM142520. Forcelli receives support as the Jerome H. Fleisch & Marlene L. Cohen Endowed Professor of Pharmacology.
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