Inhibition of MEK-ERK signaling reduces seizures in two mouse models of tuberous sclerosis complex.
Epilepsy Res
; 181: 106890, 2022 03.
Article
en En
| MEDLINE
| ID: mdl-35219048
Tuberous sclerosis complex (TSC) is a monogenic disorder characterized by hyperactivation of the mTOR signaling pathway and developmental brain malformations leading to intractable epilepsy. Although treatment with the recently approved mTOR inhibitor, everolimus, results in clinically relevant seizure suppression in up to 40% of TSC patients, seizures remain uncontrolled in a large number of cases, underscoring the need to identify novel treatment targets. The MEK-ERK signaling pathway has been found to be aberrantly activated in TSC and inhibition of MEK-ERK activity independently of mTOR rescued neuronal dendrite overgrowth in mice modeling TSC neuropathology. Here, we evaluated the efficacy of MEK-ERK inhibition on seizures in two mouse models of TSC. We found that treatment with the MEK inhibitor PD0325901 (mirdametinib) significantly reduced seizure activity in both TSC mouse models. These findings support inhibiting MEK-ERK activity as a potential alternative strategy to treat seizures in TSC.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Esclerosis Tuberosa
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Epilepsy Res
Asunto de la revista:
CEREBRO
/
NEUROLOGIA
Año:
2022
Tipo del documento:
Article