A study shows that targeting senescent cells in mTOR-related focal cortical dysplasia type II (FCDII) reduces seizures. FCDII is a neurodevelopmental disorder linked to pediatric drug-resistant epilepsy, caused by somatic mutations in the PI3K-AKT-mTOR pathway. These mutations lead to the formation of dysmorphic neurons and other abnormal cells in the brain. The study found that these pathological cells exhibit signs of cellular senescence, including p53/p16 expression, SASP, and senescence-associated β-galactosidase activity. Administration of senolytic drugs, such as dasatinib and quercetin, reduced the number of senescent cells and decreased seizure frequency in a preclinical mouse model of FCDII. The findings suggest that senotherapy could be a promising approach for treating seizures in FCDII. The study also highlights the potential of targeting mutated senescent cells in FCDII brain tissue as a therapeutic strategy. The results indicate that senolytic drugs may offer a less invasive alternative to surgical resection for treating epilepsy in FCDII patients. The study provides evidence that senescent cells contribute to epileptiform activity in FCDII and that targeting these cells can reduce seizure frequency. The research underscores the importance of understanding the role of cellular senescence in neurodevelopmental disorders and opens new avenues for the development of targeted therapies for epilepsy.A study shows that targeting senescent cells in mTOR-related focal cortical dysplasia type II (FCDII) reduces seizures. FCDII is a neurodevelopmental disorder linked to pediatric drug-resistant epilepsy, caused by somatic mutations in the PI3K-AKT-mTOR pathway. These mutations lead to the formation of dysmorphic neurons and other abnormal cells in the brain. The study found that these pathological cells exhibit signs of cellular senescence, including p53/p16 expression, SASP, and senescence-associated β-galactosidase activity. Administration of senolytic drugs, such as dasatinib and quercetin, reduced the number of senescent cells and decreased seizure frequency in a preclinical mouse model of FCDII. The findings suggest that senotherapy could be a promising approach for treating seizures in FCDII. The study also highlights the potential of targeting mutated senescent cells in FCDII brain tissue as a therapeutic strategy. The results indicate that senolytic drugs may offer a less invasive alternative to surgical resection for treating epilepsy in FCDII patients. The study provides evidence that senescent cells contribute to epileptiform activity in FCDII and that targeting these cells can reduce seizure frequency. The research underscores the importance of understanding the role of cellular senescence in neurodevelopmental disorders and opens new avenues for the development of targeted therapies for epilepsy.