Pfizer and SynapCell Present Major Preclinical Efficacy Results Using the GAERS
This article presents key preclinical data obtained through the collaboration between Pfizer and SynapCell, focusing on the evaluation of the α2/3/5-subtype-selective GABAA positive allosteric modulator PF-06372865 in the GAERS model of absence epilepsy. As a well-validated and translational model, GAERS provides highly reliable insights into the efficacy of novel antiepileptic compounds. The following sections summarize the main findings and outline the relevance of these results within the broader context of absence epilepsy research.
Background on absence epilepsy and the GAERS Model
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).
Characteristics and predictive value of the GAERS Model
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.
Preclinical evaluation of PF-06372865 by Pfizer and SynapCell
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.
Key efficacy findings in the GAERS Model
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.
Publication and presentation of the study results
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.
References:
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.