TaPPiNG-EPI · Targeting Purinergic Pathway in drug-resistant epilepsy using human Neurons and Glia.
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-04-01 → 2021-03-31
- EU contribution
- €196,591
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Targeting Purinergic Pathway in drug-resistant epilepsy using human Neurons and Glia.
Issue: Epilepsy is a neurological disorder characterized by recurrent seizures affecting affects around 65 million people worldwide and antiseizure drugs (ASDs) are routinely used to control seizures as a first line of treatment. Despite the development of many new ASDs in recent years, approximately one-third of all epilepsy cases are refractory to the existing anticonvulsants, even in combination therapy involving ASDs with different mechanisms of action. Social Impact: Given that approximately 30% of patients do not respond to available anti-seizure drugs, identification of a new pharmacological target will help to address such a significant clinical problem and therefore would have important impacts with respect to tailoring patient treatments to their needs and enhancing quality of life. The validation of a novel potential pharmacological target may prove efficient in a group of patients for whom invasive surgery is currently the only treatment choice. Objective: P2X7Rs have emerged as a potential pharmacological target to treat hyperexcitabily in animal models of brain diseases. To advance findings from animal models towards the clinical use of drugs targeting P2X7Rs for epilepsy, this project aims at using human induced pluripotent stem cell (hiPSC)-derived neurons and glia as human brain-relevant cellular models to identify a new potential pharmacological target. Conclusion: The results of this project demonstrates that i) human iPSC-derived cortical neurons and glia express functional P2X7Rs ii) establishment of an in vitro seizure model suitable for pharmacological targeting of P2X7 receptors.
Data: CORDIS, © European Union
Project objective
Epilepsy is a neurological disorder characterized by recurrent seizures affecting 65 million people worldwide of which 6 million live in Europe alone with around 30% of patients not responding to currently available treatment. The ATP-gated P2X7 receptor (P2X7R) has recently emerged as a promising target for epilepsy, showing anticonvulsant and disease-modifying properties in animal models. However, to develop P2X7R-based therapeutics the cell types involved in pathological P2X7R activation must be determined, and whether results from rodent models can be replicated in human tissue must be tested. Using human induced pluripotent stem cell-derived neurons and glia and resected brain tissue from epileptic patients, TaPPiNG-EPI proposes to investigate the cell-specific alterations and pathological contribution in the P2X7R pathway and pharmacological targeting of hyperexcitability using P2X7R antagonists. These studies will be complemented by the investigation on the alterations in P2X7R pathway in GFP-P2X7 reporter mice available in the host institution (RCSI). Through international secondments and intersectoral collaborations TaPPiNG-EPI brings together experts in purinergic signalling, industrial partners, epilepsy clinicians as well as leading European academic labs with diverse expertise. The interdisciplinary and intersectoral components of TaPPiNG-EPI combined with international collaborations and secondments in academia, the excellent training record of the supervisor and RCSI and the outstanding resources for learning and development available at RCSI will give me the tools necessary to achieve research independence and my transition to a highly employable future neuroscientist with a focus on epilepsy.
Original text from CORDIS.
Participants
- ROYAL COLLEGE OF SURGEONS IN IRELAND · DUBLIN 2CoordinatorIreland
Links
Data: CORDIS, © European Union