OV329 and GABA-aminotransferase inhibition
overview
OV329 is a next-generation GABA-aminotransferase (GABA-AT) inhibitor being developed as a potential medicine for rare and treatment-resistant forms of epilepsy and seizures. Ovid believes OV329 is significantly more potent than prior GABA-AT inhibitors which may confer seizure reduction efficacy, enhanced safety, and lower dosing.
mechanism of action
γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain and is primarily catabolized by the enzyme GABA aminotransferase (GABA-AT). Low levels of GABA in the brain have been linked to neuronal hyperexcitability, which can lead to seizures. OV329 inhibits GABA-AT activity, thereby increasing GABA levels in the brain, resulting in suppression of neuronal hyperexcitability associated with seizures. OV329 may be a best-in-class GABA-AT inhibitor that could offer enhanced efficacy with an improved benefit-risk profile.
development
OV329 is currently in a Phase 1 study with healthy volunteers to evaluate the safety, pharmacokinetic profile and target engagement associated with single and repeated oral doses of OV329. The Phase 1 study will measure two potential biomarkers for target engagement via magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS).
Prior evaluation of OV329 in preclinical seizure and epilepsy models indicate that OV329 significantly reduced focal and generalized seizures, including pharmaco-resistant seizure phenotypes. Improvement in seizure outcomes could be achieved with repeated, low dosing which have correlated with increases in brain GABA levels and tonic inhibitory neuronal signaling.
For additional information on OV329 non-clinical data, please click here.