A Novel Transposon Causes Focal Cortical Dysplasia
Focal malformations of cortical development (FMCD) are a common cause of intractable pediatric epilepsy. Some FMCD arise from gene mutations whereas others result from unknown causes. Many FMCD subtypes are associated with abnormalities in mammalian target of rapamycin (mTOR) signaling. We have recently found that the human papilloma virus 16 (HPV16) oncoprotein E6, a known activator of mTOR, is expressed in focal cortical dysplasia, a type of FMCD. These results suggest an association between HPV16 E6 and FMCD and demonstrate HPV16 E6 for the first time in the human brain. We will investigate other forms of FMCD to determine whether HPV or related viral oncoproteins can be detected. If our data is correct, the future for patients with FMCD may include targeted therapy to cure HPV16 infection that could lead to truly new and successful treatment strategies with improved efficacy (“no seizures”) and diminished morbidity (“no side effects”). Indeed, defining the molecular pathogenesis of FMCD as an infectious agent would open a cascade of ideas, experiments, and approaches that may have direct patient benefit and alter how we design therapies for intractable epilepsy.