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EpiPur SIGNED

The ATP-P2X7R axis: a target for drug-refractory epilepsy

Total Cost €

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EC-Contrib. €

0

Partnership

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 EpiPur project word cloud

Explore the words cloud of the EpiPur project. It provides you a very rough idea of what is the project "EpiPur" about.

cell    brain    excitation    hyperexcitability    network    animal    outstanding    urgent    antagonists    patients    anticonvulsant    gaps    30    p2x7    cns    skills    lacking    atp    intersectoral    mechanisms    excellent    demonstrating    mouse    tools    action    caused    showing    therapies    clinical    determined    signalling    specialised    resolution    purinergic    interdisciplinary    current    rodent    industrial    acquired    inflammation    maintained    gatekeeper    receptor    gated    filled    questions    models    tissue    learning    training    pathological    supervisor    me    contribution    record    neuroinflammatory    ineffective    subcellular    epilepsy    expression    elucidate    mediating    experts    disease    clinicians    give    seizures    answers    resected    lines    human    p2x7r    transgenic    temporal    progression    host    epipur    modifying    replicated    release    independence    types    rcsi    sustained    sensitivity    newly    inhibition    team    add    vivo    disorders    emerged    glial    biosensors    tested    activation    brings   

Project "EpiPur" data sheet

The following table provides information about the project.

Coordinator
ROYAL COLLEGE OF SURGEONS IN IRELAND 

Organization address
address: Saint Stephen's Green 123
city: DUBLIN
postcode: 2
website: www.rcsi.ie

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Ireland [IE]
 Total cost 175˙866 €
 EC max contribution 175˙866 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-01-01   to  2020-01-12

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ROYAL COLLEGE OF SURGEONS IN IRELAND IE (DUBLIN) coordinator 175˙866.00

Map

 Project objective

Current epilepsy therapies, based on mediating excitation or inhibition have no impact on disease progression and are ineffective in over 30% of patients, demonstrating the urgent need for therapies with different mechanisms of action. An exciting concept is that increased hyperexcitability states and network changes are caused and maintained by a sustained glial activation.The ATP-gated P2X7 receptor (P2X7R), a gatekeeper of inflammation, has recently emerged as a promising target for epilepsy, showing anticonvulsant and disease-modifying properties in animal models. To bring P2X7R further towards a clinical application, however, important gaps in our understanding must be filled. Evidence for ATP release in the brain during seizures is currently lacking, 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. Recent technical advances now bring the answers to these questions within reach. EpiPur brings together a team of experts in purinergic signalling, industrial partners specialised in the development of P2X7R antagonists and epilepsy clinicians. Biosensors will be used to record ATP in vivo with high sensitivity and temporal resolution; new transgenic mouse lines will be used to elucidate the subcellular expression and cell-specific disease contribution of P2X7R. Newly developed P2X7R antagonists will be tested in brain tissue resected from epilepsy patients. This highly interdisciplinary and intersectoral approach will add a significant contribution to the understanding of neuroinflammatory processes in disorders of the CNS. Further, the skills acquired during the research project, the excellent training record of the supervisor and host institution and the outstanding resources for learning and development available at RCSI will give me the tools necessary to achieve research independence.

 Publications

year authors and title journal last update
List of publications.
2018 Mariana Alves, Edward Beamer, Tobias Engel
The Metabotropic Purinergic P2Y Receptor Family as Novel Drug Target in Epilepsy
published pages: , ISSN: 1663-9812, DOI: 10.3389/fphar.2018.00193
Frontiers in Pharmacology 9 2020-04-15
2018 Edward H. Beamer, Jeronimo Jurado-Arjona, Eva M. Jimenez-Mateos, James Morgan, Cristina R. Reschke, Aidan Kenny, Gioacchino de Leo, Luis A. Olivos-Oré, Marina Arribas-Blázquez, Stephen F. Madden, Jesús Merchán-Rubira, Norman Delanty, Michael A. Farrell, Donncha F. O’Brien, Jesus Avila, Miguel Diaz-Hernandez, M. Teresa Miras-Portugal, Antonio R. Artalejo, Felix Hernandez, David C. Henshall, T
MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus
published pages: , ISSN: 1662-5099, DOI: 10.3389/fnmol.2018.00442
Frontiers in Molecular Neuroscience 11 2020-04-15
2018 Tobias Engel, Raquel Gómez-Sintes, Mariana Alves, Eva M. Jimenez-Mateos, Marta Fernández-Nogales, Amaya Sanz-Rodriguez, James Morgan, Edward Beamer, Alberto Rodríguez-Matellán, Mark Dunleavy, Takanori Sano, Jesus Avila, Miguel Medina, Felix Hernandez, José J. Lucas, David C. Henshall
Bi-directional genetic modulation of GSK-3β exacerbates hippocampal neuropathology in experimental status epilepticus
published pages: , ISSN: 2041-4889, DOI: 10.1038/s41419-018-0963-5
Cell Death & Disease 9/10 2020-04-15

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