PRX2904 / Praxis Precision Medicines - LARVOL DELTA

Block of Slack (KCNT1) ameliorates loss of non-synaptic mitochondrial function after traumatic brain injury (Neuroscience 2025) - "Behavioral experiments indicated that pharmacological treatments targeting Slack potassium channels may ameliorate at least some of the effect of traumatic brain injury. Ongoing experiments will investigate PRX-2904 repeated dosing and the therapeutic window of intervention further."

CNS Disorders • Epilepsy • Vascular Neurology

Loss or block of Slack channels prevents long-term potentiation (Neuroscience 2025) - "In addition, treating wild-type neurons with the Slack inhibitor PRX-2904 starting 30 minutes before stimulation also prevented the increase of GluR1 intensity after stimulation. These results support a model where Slack activity plays a direct role in the short-term maintenance of LTP. Slack channels have been shown to regulate local protein synthesis by binding regulators of mRNA translation, and we are currently testing the hypothesis that loss of this activity-dependent translation leads to the observed loss of long-term synaptic potentiation."

CNS Disorders • Cognitive Disorders • Epilepsy • Mental Retardation

Kna1.1 antagonism with PRX2904 suppresses epileptiform activity due to a heterozygous mutation in Kcnt1 (Neuroscience 2022) - "Kcnt1+/R455H mice were tested with pentylenetetrazole (PTZ) 50 mg/kg IP administered 1 or 2 hours after administration of either PRX2904 75 mg/kg SC or vehicle control. Baseline epileptiform spike rates on EEG were variable between animals, but there was a marked per-animal reduction in the 24 hours following PRX2904 administration (p=0.005, N=12). These results suggest that KNa1.1 antagonists may be an effective treatment for KCNT1 epilepsy."

CNS Disorders • Epilepsy • Psychiatry • PRDX2