Epilepsy is the most common chronic neurological disorder, affecting over 50 million people worldwide.
Major challenges in treating epilepsy include pharmacoresistance , adverse drug effects, correct diagnosis of seizures and prognosis of epilepsy.
Currently available anti-epileptic drugs (AEDs), when effective, are symptomatic with no effect on disease progression. Mounting evidence demonstrates a causal role for neuroinflammation during both seizure generation and epileptogenesis.
The ATP-gated P2X7 receptor (P2X7) is a key driver of inflammation and links glial-driven pro-inflammatory signalling to hyperexcitability. Data produced by the group, using animal models, demonstrates potent anticonvulsive and antiepileptogenic properties of P2X7 antagonists and, critically, suggests a disease-modifying potential for P2X7 antagonism.
To further advance P2X7 targeting into the clinic, however, we must establish signalling pathways downstream of P2X7 and test the effectiveness of novel, brain stable P2X7 antagonists in both animal models relevant to the human condition and patient tissue. Further, biomarkers must be identified for predicting disease progression and treatment success and identifying patients who may benefit from P2X7 antagonists.
To tackle these challenges, our group will employ a multidisciplinary approach making use of newly developed mouse models, highly specific brain stable P2X7 antagonists and diagnostic devices which will be tested in patients.