Poster Presentation 16th Asian Conference on Transcription 2019

Using Xenous laevis tadpole as a model for testing anti-inflammatory drugs as treatment for intractable epilepsy. (1095)

Sulagna Banerjee 1 , Erin Damsteegt 1 , Paul Szyszka 1 , Caroline Beck 1
  1. University of Otago, Dunedin, OTAGO, New Zealand

Epileptic encephalopathies are a group of catastrophic seizure syndromes often caused by de novo genetic mutations. Seizures typically manifest before 1 year of age, and patients often develop developmental and intellectual disabilities. They are at risk of sudden unexpected death and about 25% of the children die before the age of 20 years. One third of patients also develop drug resistance, where the patient’s seizures cannot be managed through conventional anti-epileptic drugs, and only a few can be treated by brain surgery.  In search of alternative therapy targets, current epilepsy research has put the spotlight on neuroinflammation. There is a correlation between brain inflammation and epileptogenesis, as well as worsening of the epileptic conditions. Anti-inflammatory drugs (AIDs) have shown disease modifying effects in some rat models. Here we test the hypothesis that inhibiting pro-inflammatory pathways reduces epileptic seizures in Xenopus laevis tadpoles – an epilepsy model which is more easily accessible to genetic manipulation than rats. We use behavioural and electrophysiological assays to quantify epileptic seizures in this model. We first established the effects of AIDs like Losartan in the Pentylenetetrazol induced status epilepticus model of epilepsy. We are now developing Xenopus laevis epileptic encephalopathy models using CRISPR/Cas9 to induce gene alterations mimicking those found in human patients. We hope that with our model of intractable epilepsy, we can have a better understanding of how targeting neuroinflammation may help in reducing the severity of the seizures in these chronic conditions.