Selene Therapeutics Ltd.

Selene Therapeutics is pioneering a new therapeutic strategy for treating refractory epilepsy – regulation of the neuronal activity set point by reduction of the neuronal mean firing rate (MFR). Selene aims to develop small molecule for inhibitors of Dih

DHODH as a novel target for epilepsy treatment A regulated homeostatic system is characterized by a set point, a physiological state held constant by various mechanisms, through sensors that detect deviations from it and effectors that precisely retarget to it via negative feedback. Neuronal activity is regulated by multiple homeostatic mechanisms that are necessary to ensure stable neuronal and network function. In silico transcriptome metabolic modeling revealed mitochondrial DHODH as a leading target that secures metabolic homeostasis of hyperexcitable hippocampal circuits. Inhibition of DHODH decreased the average level of spontaneous neuronal spiking activity, known as the mean firing rate (MFR). Mitochondria play a critical role in energy metabolism and Ca2+ homeostasis in neurons. Under DHODH blockade Homeostatic responses of the MFR to activity perturbations were maintained, and MFR was identified as a potential set point of this homeostatic systems.

Hospitals, Healthcare providers