Targeting the purinergic system for disease-modification in epilepsy

Current epilepsy therapies, based on mediating excitation or inhibition, are ineffective in 30% of patients & have no impact on disease progression, demonstrating an urgent need for new therapies.

Mounting evidence showed the therapeutic potential of targeting the purinergic system during epilepsy with the disease-modifying effects observed via targeting the P2X7 receptor & Adenosine kinase (ADK) being a promise. P2X7 & ADK are increased in the brain in experimental models of epilepsy and in patient brain.

Further, data showed anticonvulsive & anti-epileptogenic potential of targeting P2X7 or ADK.

To advance these findings towards a clinical application, results must be replicated in animal models mimicking closer the human condition (e.g.TBI model) and effects must be tested in human cells (hiPSC).

Importantly, while there is now compelling evidence demonstrating the therapeutic potential of targeting both P2X7 & ADK separately, a combined treatment, targeting both simultaneously, may lead to better seizure control & suppression of epilepsy.

By using relevant animal models of epilepsy and hiPSC, EpiPurines will establish the disease-modifying potential of targeting different components of the purinergic system during epileptogenesis, thereby establishing P2X7 & ADK-targeting as potential treatment for epilepsy.

To achieve this, EpiPurines brings together, for the first time, a team of experts in purinergic signaling from different research fields (Adenosine & ATP-signalling) & industrial partners.

This highly interdisciplinary & intersectoral approach will contribute significantly to the understanding of purinergic signalling during seizures & epilepsy providing novel therapeutic approaches.

The skills acquired during the research project, the excellent training record of the supervisors & host institutions and the outstanding resources for learning & development available at RCSI & RU will give me the tools necessary to become a highly employable neuroscientist.