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Targeting the purinergic system for disease-modification in epilepsy

Descrizione del progetto

Nuovi bersagli terapeutici nell’epilessia

L’epilessia è una condizione neurologica caratterizzata da convulsioni. Le attuali terapie sono inefficaci in quasi il 30 % dei pazienti, rendendo necessario lo sviluppo di nuovi trattamenti. Il progetto EpiPurines, finanziato dall’UE, si sta concentrando sul sistema di segnalazione purinergico, attivato da nucleotidi e nucleosidi. Utilizzando modelli animali di malattie e cellule staminali pluripotenti indotte, gli scienziati studieranno l’esito del targeting di vari recettori ed enzimi implicati nei percorsi del sistema. I risultati ci aiuteranno a comprendere il ruolo della segnalazione purinergica nell’epilettogenesi e apriranno la strada a nuovi farmaci in grado di offrire un migliore controllo delle crisi e la soppressione dell’epilessia.

Obiettivo

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.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Invito a presentare proposte

(si apre in una nuova finestra) H2020-MSCA-IF-2020

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Coordinatore

ROYAL COLLEGE OF SURGEONS IN IRELAND
Contributo netto dell'UE
€ 257 561,28
Indirizzo
ST STEPHEN GREER 123
D02 YN77 DUBLIN 2
Irlanda
Regione
Ireland Eastern and Midland Dublin
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 257 561,28

Partner (1)