2. Academic Validation
  3. Inhibition of MEK-ERK signaling reduces seizures in two mouse models of tuberous sclerosis complex

Inhibition of MEK-ERK signaling reduces seizures in two mouse models of tuberous sclerosis complex

  • Epilepsy Res. 2022 Mar;181:106890. doi: 10.1016/j.eplepsyres.2022.106890.
Lena H Nguyen 1,  Steven C Leiser 2,  Dekun Song 2,  Daniela Brunner 3,  Steven L Roberds 3,  Michael Wong 4,  Angelique Bordey 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA; Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA.
  • 2 Department of Translational EEG, PsychoGenics, Inc., Paramus, NJ, USA.
  • 3 Tuberous Sclerosis Alliance, Silver Spring, MD, USA.
  • 4 Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
  • 5 Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA; Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA. Electronic address: angelique.bordey@yale.edu.
PMID: 35219048 DOI: 10.1016/j.eplepsyres.2022.106890
Abstract

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.

Keywords

Epilepsy; MAPK; MEK inhibitor; MEK-ERK signaling; Seizures; Tuberous sclerosis complex.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z