Boston, Mass., December 6 – Epilepsy is common among patients with tuberous sclerosis complex (TSC). Scientists are zeroing-in on the mechanisms behind TSC development and devising methods to identify which patients will or will not have seizures. In these and other related studies, investigators have identified potential therapeutic targets and a compound—rapamycin—that may have a therapeutic role in TSC, pretzel syndrome and other epilepsies. They are presenting their findings at the American Epilepsy Society annual meeting here.
Patients with TSC may have one of two genetic forms of the condition identified as TSC1 and TSC 2. Researchers at Wayne State University measured tryptophan metabolism in brain tissue following surgery in 12 patients with TSC and discovered differences in the effect of inflammation on abnormalities in tissue removed from the brain. Epileptogenic tubers showed higher expression of indoleamine 2,3-dioxygenase (IDO) compared to tubers which are not epileptogenic. In addition, tissue from patients with TSC2 mutations had higher expression of a substance called major vault protein (MVP).
“Higher expression of MVP in patients with TSC2 may be related to a more severe course of the disease compared to patients with TSC1,” the study authors report. “IDO and MVP might represent novel therapeutic targets for patients with TSC and may be individualized for the type of mutation.”
In collaborative studies at Baylor College of Medicine and Rutgers University, researchers have found that the immunosuppressant drug rapamycin significantly reversed neuronal cell damage and reduced epileptiform brain wave activity in a model for cortical dysplasia. The investigators suggest “that rapamycin may function as a novel treatment for some forms of epilepsy.”
Another study reported at this meeting suggests that rapamycin might have a therapeutic role in pretzel syndrome (PS), a genetic disorder in Old Order Mennonite children that causes intractable epilepsy. Investigators at the University of Pennsylvania conducted studies to characterize the pathogenic mechanisms underlying the genetic mutation responsible for the disorder.
The team modeled PS in vitro and in laboratory animals, and analyzed the cascade of chemical events leading to the abnormality in brain development associated with this syndrome. They also report they have prevented the characteristic abnormality by treatment with rapamycin. According to the investigators, “These studies, for the first time, delineate a functional role of a protein called STRAD alpha during cortical development and suggest a potential therapeutic role of rapamycin in PS.”