BOSTON—Patients with tuberous sclerosis complex (TSC) may benefit from novel therapies targeting idoleamine 2,3-dioxygenase (IDO) and major vault protein (MVP), researchers at Wayne State University in Detroit reported at the American Epilepsy Society meeting. Carlos Batista, a graduate student in the Translational Neuroscience Program, and colleagues studied cortical tubers that were surgically removed from 12 children with TSC and found elevated tryptophan metabolism and expressions of IDO and MVP.
“Cortical tubers express large numbers of activated microglia, macrophages, and T lymphocytes, thus suggesting activation of inflammatory pathways,” the researchers noted. “Under conditions that cause activation of inflammatory pathways, IDO (the rate-limiting enzyme of tryptophan metabolism by the kynurenine pathway in the brain) is induced by IFN-γ.”
Furthermore, MVP, which is associated with multidrug resistance, is also induced by IFN-γ. Researchers hypothesized and found that the effect of inflammation on MVP and IDO in epileptogenic tumors may be different in TSC1 and TSC2 mutations. Patients with TSC2 had a higher expression of MVP than those with TSC1, which may explain the more severe course of the disease in TSC2 patients.