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Targeting Purinergic Pathway in drug-resistant epilepsy using human Neurons and Glia.

Project description

A novel target for epilepsy treatment

Epilepsy affects millions of people worldwide nearly a third of which do not respond to available treatments for controlling the recurrent seizures. The ATP-gated P2X7 receptor (P2X7R) has spurred great interest as a new therapeutic target for epilepsy, but first, the cells associated with pathological P2X7R activation must be identified. For this purpose, the EU-funded TaPPiNG-EPI project will use human-induced pluripotent stem cell-derived neurons and glia, as well as resected brain tissue from patients with epilepsy, to investigate the cell-specific alterations linked with the P2X7R pathway. Pharmacological targeting of the pathway using specific drugs will unveil the therapeutic potential of P2X7R in epilepsy.

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.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

ROYAL COLLEGE OF SURGEONS IN IRELAND
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 196 590,72
Address
ST STEPHEN'S GREEN 123
2 DUBLIN
Ireland

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 196 590,72
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