How can the molecular defects underlying GABAB receptor variant developmental and epileptic encephalopathy be reversed?
Our results show that correction of presynaptic hyperexcitability by positive allosteric modulation of GABAB receptors could be a viable therapeutic strategy for GABAB receptor epilepsies.
Presynaptic hyperactivity due to expression GABAB receptor variant S695I
Using Ca2+ imaging of GCaMP6f fused to synaptophysin we report presynaptic hyperexcitability ensues due to expression of S695I
Correction of presynaptic hyperexcitability by positive allosteric modulation of GABAB receptors
The presynaptic hyperexcitability can be reversed by the application of a GABAB receptor positive allosteric modulator demonstrating the therapeutic potential of this approach for treatment of GABAB receptor epilepsy.
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M Minere, M Mortensen, V Dorovykh, G Warnes, D Nizetic, TG Smart* & SB Hannan* (2024). Presynaptic hyperexcitability reversed by positive allosteric modulation of a GABABR epilepsy variant. Brain, awae232
*corresponding authors
Saad Hannan 