Epilepsy is a common neurological disorder characterised by recurrent seizures due to the hyperexcitability and hypersyncrhonisation of neurons. Among the different epileptic syndromes, Mesial Temporal Lobe Epilepsy (MTLE) is the most common. Several recent studies using animal models have shown that a strong neuroinflammation occurs during MTLE leading to neurodegeneration of specific populations of neurons in the hippocampus as well as neuronal excitability and occurrence of spontaneous seizures.
Drugs currently available for the treatment of epilepsy targeting neuroinflammation process (steroids, plasmapheresis or intravenous immunoglobulin injection) have shown varying effects in randomized controlled clinical trial.
Role of NOX enzymes
In parallel, oxidative stress has emerged as a key factor that, similarly to neuroinflammation, not only occurs acutely as a result of status epilepticus, but contributes to epileptogenesis and chronic epilepsy. A pilot study recently performed by Neurinox partners showed a strong upregulation of NOX2 in the hippocampus of an animal model of MTLE-HS.
The expression of NOX enzymes increased concomitantly with the establishment of chronic inflammatory phase. In addition, a substantial increase in NOX2 in the microglia was observed in the cortex of an epileptic patient. Today, efficient MTLE-HS treatment does not exist and NEURINOX will focus on this poorly explored aspect of epilepsy.
Work planned in Neurinox
Among the different animal models of MTLE, the unilateral intra-hippocampal injection of kainate (a glutamatergic excitotoxin) in mice has recently emerged. This injection into a specific brain region initially induces a focal status epilepticus. This is followed by a latent period of two weeks during which neurodegeneration and neuroinflammation are observed, as well as the progressive development of recurrent spontaneous hippocampal electrical discharges. The objective of Neurinox is to address the question whether inhibiting NOX enzymes (both genetically and pharmacologically) in rodent models is beneficial for the development of MTLE-HS.
Surgery to remove the brain area where epileptic seizures originate is a therapeutic option. Neurinox will have access to unique brain material from patients with MTLE-HS. This material will be compared with surrounding tissues to detect proteins, genes or molecules involved in NOX-mediated oxidation pathways.
www.epilepsy.com: A platform for information to patients, health professionals and researchers regarding epilepsy, treatments and ongoing research.
www.epilepsyfoundation.org: The website of the Epilepsy foundation gives information about the disease but also about different initiatives in research and possible funding and grant opportunities for researchers.
The NEURINOX project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n°278611