Absence epilepsy is a form of epileptic syndrome where patients show generalized non-convulsive seizures characterized by a brief unresponsiveness to environmental stimuli and cessation of activity. In human, typical absence seizures are associated with bilateral, synchronous and regular spike-and-wave discharges (SWD). SynapCell World-exclusive model, the Genetic absence epilepsy rat from Strasbourg (GAERS) displays spontaneous SWD and has become a reference model for the past thirty years.
The GAERS shows behavioral, electrophysiological and pharmacological features of absence seizures with a pharmacology that perfectly mirrors human absence seizures.
Pfizer has developed PF-06372865 a new subtype-selective GABAA positive allosteric modulator, and selected SynapCell for the preclinical in vivo evaluation of the antiepileptic potential of its compound.
The investigations revealed that PF-06372865 dose-dependently reduced the occurrence of SWD in the GAERS model with a significant effect at 1, 3 and 10 mg/kg. In comparison to the reference compound diazepam, PF-06372865 has a slower peak time effect but a longer efficacy.
In addition, PF‐06372865 demonstrated robust efficacy in suppressing SWDs in the GAERS model of absence epilepsy. To our knowledge, this is the first demonstration of antiepileptic activity of an α2/3/5‐subtype‐selective GABAA PAM in a model of absence epilepsy. Further study of the antiepileptic properties of PF‐06372865 is warranted in patients with absence seizures.
The significant outcomes of this study have been published in a joint scientific paper ( Duveau et al, CNS Neurosci Ther. 2018) and will be presented at the Society for Neuroscience Annual Conference Neuroscience 2018 (Poster n°289.15) in San Diego.
Duveau V, Buhl D, Evrard A, Ruggiero C, Mandé-Niedergang B, Roucard C, Gurrell R. Pronounced antiepileptic activity of the subtype‐selective GABAA‐positive allosteric modulator PF‐06372865 in the GAERS absence epilepsy model. CNS Neurosci Ther. 2018.