4M Therapeutics Inc. has announced the presentation of preclinical data on its small-molecule glycogen synthase kinase-3β (GSK-3β) inhibitors in models of bipolar disorder.

The study examined the effects of 4M’s GSK-3β inhibitors 4MT-A and 4MT-B on amphetamine (AMP)-induced positive appetitive ultrasonic vocalizations (USVs), a validated model of positive affective state. Marked increases in USVs when treated with AMP were attenuated by lithium, and equal or greater reduction in USVs was observed when treated with 4MT-A and 4MT-B at 1/500th to 1/1000th the concentration of lithium. Similar patterns were observed across USV categories and treatment groups in both the first and second hour after AMP dosing. Supporting data showed target engagement for 4MT-A through the reduction of pCRMP2 in vitro in excitatory cortical neurons and in vivo in rat brain. These statistically significant reductions in pCRMP2 demonstrated GSK-3β inhibition affecting a key biomarker.

4M is on track to initiate a phase I trial with its lead investigational compound next year (4M Therapeutics News Release).