An Emerging Role for Sigma-1 Receptors in the Treatment of Developmental and Epileptic Encephalopathies.
Int J Mol Sci
; 22(16)2021 Aug 05.
Article
in En
| MEDLINE
| ID: mdl-34445144
ABSTRACT
Developmental and epileptic encephalopathies (DEEs) are complex conditions characterized primarily by seizures associated with neurodevelopmental and motor deficits. Recent evidence supports sigma-1 receptor modulation in both neuroprotection and antiseizure activity, suggesting that sigma-1 receptors may play a role in the pathogenesis of DEEs, and that targeting this receptor has the potential to positively impact both seizures and non-seizure outcomes in these disorders. Recent studies have demonstrated that the antiseizure medication fenfluramine, a serotonin-releasing drug that also acts as a positive modulator of sigma-1 receptors, reduces seizures and improves everyday executive functions (behavior, emotions, cognition) in patients with Dravet syndrome and Lennox-Gastaut syndrome. Here, we review the evidence for sigma-1 activity in reducing seizure frequency and promoting neuroprotection in the context of DEE pathophysiology and clinical presentation, using fenfluramine as a case example. Challenges and opportunities for future research include developing appropriate models for evaluating sigma-1 receptors in these syndromic epileptic conditions with multisystem involvement and complex clinical presentation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Diseases
/
Receptors, sigma
/
Epileptic Syndromes
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2021
Document type:
Article