A new study links temporal lobe epilepsy to early aging in brain support cells, showing that clearing these cells in mice reduces seizures and improves memory. Researchers at Georgetown University Medical Center used existing drugs to achieve these results, offering potential for faster treatments in humans. The findings, published on December 22, highlight hope for patients resistant to current medications.
Temporal lobe epilepsy (TLE), the most common form unresponsive to drugs and affecting about 40% of epilepsy patients, often stems from causes like head injuries, infections, tumors, or genetic issues. It disrupts memory and cognition alongside repeated seizures. A study from Georgetown University Medical Center reveals that TLE involves accelerated aging in glial cells, which support neurons without generating electrical signals.
Examining human brain tissue from TLE surgery patients, researchers found a five-fold rise in senescent glial cells compared to non-epilepsy autopsy samples. In a mouse model mimicking TLE via brain injury, markers of cellular aging appeared within two weeks.
Clearing these senescent cells proved effective. Using genetic methods and drugs, the team reduced senescent cells by roughly 50%. Treated mice showed normal performance in maze memory tests, fewer seizures, and about one-third avoided epilepsy entirely.
The drugs—dasatinib, an FDA-approved leukemia treatment, and quercetin, a flavonoid from plants with antioxidant properties—have established safety profiles and are in trials for other conditions. Senior author Patrick A. Forcelli, Ph.D., noted, "A third of individuals living with epilepsy don't achieve freedom from seizures with current medications." He added that senotherapy might reduce surgery needs or enhance outcomes.
First co-authors Tahiyana Khan, Ph.D., and David J. McFall linked glial aging to normal brain aging and Alzheimer's disease. Forcelli mentioned ongoing research into intervention timing and other repurposed drugs for epilepsy models, aiming for clinical applications.
Funded by the National Institutes of Health, the study appeared in Annals of Neurology on December 22. Authors reported no financial conflicts.
