Restoring the brain’s natural rhythms by modulating overactive T-type calcium channels

Calcium and ion channels play a critical role in neuronal signaling.  T-type calcium channels (Cav3.1, 3.2, & 3.3) respond to small membrane depolarizations and gate the activity of additional ion channels whose activation results in the firing of neurons.  Cav3’s finely-tuned voltage-gated property and pacemaker function mediates the transition from tonic to bust-firing and generates neural “oscillations” between brain nuclei and across their pathways.

The transition to burst-firing and abnormal oscillatory pattern occurs in a number of neurologic disorders, including essential tremor, Parkinson’s disease, dystonia, epilepsy, pain, and schizophrenia and rare, pediatric genetic disorders, such as Angelman Syndrome. These diseases are mediated by Cav3, a common pathophysiologic pathway.  Central and peripheral biomarkers facilitate in vivo readouts of dysrhythmia s and target modulation with Cavion’s Cav3 therapies.

Despite substantial interest in Cav3 as a target, to date there has been little chemistry progress made to improve upon existing, prototype Cav3 modulators which demonstrate clinical validation, but are limited as chronic therapeutics. These limitations have hampered the full exploration of the utility of Cav3 modulators.   With CX-8998, Cavion possesses a potential best-in-class Cav3 modulator with a superior potency, selectivity and a favorable safety and tolerability profile. CX-8998 is currently being investigated in Phase 2 clinical studies.