Inhibition of oxidative stress as target of mechanisms of epileptogenesis in PIGA related developmental and epileptic encephalopathy.

This project has been approved for funding - the activation procedure is still pending

PIGA-related developmental epileptic encephalopathy (DEE) (OMIM #300868) is a recently recognized rare neurological disorder characterized by severe intellectual disability, refractory seizures and early death.
During epileptogenesis many molecular, cellular and functional modifications occur in the brain, including neuroinflammation and oxidative stress, which contributes to seizure recurrence, excitotoxicity and neuronal death. Recently, it has been demonstrated that the combination of N-acetylcysteine and sulforaphane normalize the level of oxidative stress markers, namely GSH and GSSG and GSH redox ratio (GSH/GSSG) in a model of acquired epilepsy.
Aim of this study is to repurpose two safe antioxidant drugs, namely N-acetylcysteine and sulforaphane, as add-on treatment in patients with PIGA-related DEE in order to control intractable seizures and to improve the deficit in cognitive and behavioral performances.
The use of N-acetylcysteine and sulforaphane, might have effect in reducing seizure frequency and improving cognitive and behavioral disturbances in PIGA-related DEE. If this hypothesis holds true, considering the role of oxidative stress and inflammation in epileptogenesis, these therapies might be extended in the future to other severe forms of DEEs.