BioCentury
ARTICLE | Distillery Therapeutics

Aubagio and other DHODH inhibitors as epilepsy therapies

May 20, 2019 8:54 PM UTC

INDICATION: Epilepsy

Patient sample, cell culture and mouse studies suggest inhibiting DHODH could help treat epilepsy. Metabolic modeling of transcriptome data from the cortex and hippocampus of epilepsy patients and two rat models of epilepsy, followed by in silico screening of metabolic gene knockouts in the model, identified DHOHD as a target whose deficiency could restore a normal metabolic state. In primary mouse hippocampal neurons treated with the seizure-inducing compound pentylenetetrazole (PTZ), the DHODH inhibitor Aubagio teriflunomide decreased mitochondrial calcium levels, which are associated with seizure activity, compared with vehicle. In a mouse model of chemical-induced epilepsy, Aubagio decreased clinical disease scores and incidence of seizures. In a mouse model of Dravet syndrome, a form of childhood epilepsy, Aubagio decreased the incidence of thermally-induced seizures. Next steps could include testing other DHODH inhibitors in models of epilepsy...

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