Filamin A inhibition reduces seizure activity in a mouse model of focal cortical malformations
Longbo Zhang, Tianxiang Huang, Shannon Teaw, Lena H. Nguyen, Lawrence S. Hsieh, Xuan Gong, Lindsay H. Burns, Angélique Bordey
Abstract
knockdown reduced seizure frequency independently of mTOR signaling. Treating mice with a small molecule targeting FLNA, PTI-125, before the onset of seizures alleviated neuronal abnormalities and reduced seizure frequency compared to vehicle-treated mice. In addition, the treatment was also effective when injected after seizure onset in juvenile and adult mice. These data suggest that targeting FLNA with either short hairpin RNAs or the small molecule PTI-125 might be effective in reducing seizures in patients with TSC and FCDII bearing mutations in PI3K-Rheb pathway genes.
Topics & Concepts
FilaminCortical dysplasiaTuberous sclerosisNeuroscienceFLNAEpilepsyMedicinePathologyBiologyGeneticsCytoskeletonCellTuberous Sclerosis Complex ResearchEpilepsy research and treatmentCerebrospinal fluid and hydrocephalus