mTOR-therapy and targeted treatment opportunities in mTOR-related epilepsies associated with cortical malformations - 07/04/23
, S. Baulac dHighlights |
• | mTOR signaling pathway is upregulated in tuberous sclerosis complex (TSC)- and FCD-related epilepsy. |
• | Somatic mutations in genes of the mTOR pathway cause cortical malformations. |
• | mTOR inhibitors are explored for possible antiseizure effects. |
• | One phase III study to date established the efficacy of everolimus in TSC-related epilepsy. |
• | Several open studies, that still need to be confirmed, showed encouraging results for mTOR inhibitors as antiseizure medications. |
Abstract |
Dysregulation of the mTOR pathway is now well documented in several neurodevelopmental disorders associated with epilepsy. Mutations of mTOR pathway genes are involved in tuberous sclerosis complex (TSC) as well as in a range of cortical malformations from hemimegalencephaly (HME) to type II focal cortical dysplasia (FCD II), leading to the concept of “mTORopathies” (mTOR pathway-related malformations). This suggests that mTOR inhibitors (notably rapamycin (sirolimus), and everolimus) could be used as antiseizure medication. In this review, we provide an overview of pharmacological treatments targeting the mTOR pathway for epilepsy based on lectures from the ILAE French Chapter meeting in October 2022 in Grenoble. There is strong preclinical evidence for the antiseizure effects of mTOR inhibitors in TSC and cortical malformation mouse models. There are also open studies on the antiseizure effects of mTOR inhibitors, as well as one phase III study showing the antiseizure effect of everolimus in TSC patients. Finally, we discuss to which extent mTOR inhibitors might have properties beyond the antiseizure effect on associated neuropsychiatric comorbidities. We also discuss a new way of treatment on the mTOR pathways.
Le texte complet de cet article est disponible en PDF.Keywords : Epilepsy, Focal cortical dysplasia, Tuberous sclerosis complex, Rapamycin, Everolimus, Sirolimus, mTOR signaling pathway
Plan
Vol 179 - N° 4
P. 337-344 - avril 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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