Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age

Abstract

Introduction: Mechanistic target of rapamycin (mTOR) inhibitors sirolimus and everolimus are an effective therapy for subependymal giant cell astrocytomas, cardiac rhabdomyomas, renal angiomyolipomas, and lymphangioleiomyomatosis associated with tuberous sclerosis complex (TSC). Everolimus was recently approved in the EU and the USA for the treatment of refractory focal-onset seizures. Despite frequent use of mTOR inhibitors, there are only a few studies on their effect on epilepsy control in children under 2 years of age. This study aims to assess the effect of adjunctive mTOR

Diagnóstico prenatal de esclerosis tuberosa en asociación con rabdomiomas: comunicación de caso y discusión de la importancia del diagnóstico molecular

“…Se encuentran en estudio los inhibidores mTOR para la prevención y tratamiento de epilepsia en niños con CET (18) , lo cual aumenta la importancia en hacer el diagnóstico temprano de tuberosis esclerosa, en especial en la población asintomática.…”

Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease

“…Recently, the retrospective analysis of TSC patients treated with everolimus or sirolimus under the age of 2 years has reported promising benefits on epilepsy. 191 This study for the basis for the testing of mTOR inhibition in a large cohort of patients with TSC. The mTORC1 activation in tissue stems promoted mRNA translation near synapses which required neuronal circuit formation.…”

mTOR Signaling: Recent Progress

“…mTOR is mechanistically tightly interconnected with the TSC1/TSC2 complex; therefore, it has been found upregulated in patients with TSC—an autosomal dominant disorder caused by loss-of-function mutations of either TSC1 or TSC2 genes—who develop neurological manifestations, including epilepsy, neuropsychiatric disorders, autism, and brain tumors [ 20 , 21 ]. mTOR inhibition in TSC patients is promising against epilepsy, whereas mTORC1-associated autophagy has been correlated with neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease [ 22 , 23 , 24 ]. mTOR signaling is also engaged in the regulation of cardiac physiology and corresponding cardiovascular maladies.…”