Fast-spiking, parvalbumin-positive GABAergic interneurons in corticolimbic circuits modulate the synchronous firing of pyramidal neurons to enhance gamma-frequency oscillations which are thought to underpin cognitive function. Increasing evidence from post-mortem studies and animal models suggest that reduced activity of this class of interneuron may contribute to schizophrenia.
Phase 1a study results support the cognitive safety, and potential efficacy, of AUT00206, a potent and selective modulator of Kv3.1 and Kv3.2 voltage-gated potassium channels in healthy volunteers using schizophrenia-relevant cognitive tests. The interim analysis of the phase 1b CANTAB data, an exploratory endpoint, in about 2/3 of the intended sample support previous findings that patients with schizophrenia are heterogeneous. In light of this finding, we will explore the data for correlations between baseline cognitive performance and treatment outcome.