FLNA identified as a target for epilepsy associated with focal cortical dysplasia type II

INDICATION: Epilepsy

Inhibiting the actin-binding protein FLNA could prevent or treat epilepsy associated with focal cortical dysplasia type II, a cerebral developmental malformation. Levels of FLNA protein in cortical tissue from 12 patients with focal cortical dysplasia type II who had undergone surgery for epilepsy than in tissue from 11 age-matched healthy controls who had surgery for brain trauma. In a mouse model of focal cortical dysplasia type II, an shRNA against FLNA lowered seizure frequency by 83% and prevented disease-associated neuronal misplacement, soma size enlargement and dendritic dysmorphogenesis. In the same model, the small molecule FLNA inhibitor PTI-125 given before or after seizure onset lowered neuronal soma size, decreased dendritic dysmorphogenesis and reduced seizure frequency by 73% or 69%, respectively. Ongoing work includes testing undisclosed FLNA inhibitors in models of other epilepsy disorders...