DESIRE
"Development and Epilepsy - Strategies for Innovative Research to improve diagnosis, prevention and treatment in children with difficult to treat Epilepsy"
| Coordinatore | UNIVERSITA DEGLI STUDI DI FIRENZE
Organization address
address: Piazza San Marco 4 contact info |
| Nazionalità Coordinatore | Italy [IT] |
| Sito del progetto | http://epilepsydesireproject.eu/ |
| Totale costo | 16˙452˙657 € |
| EC contributo | 11˙995˙646 € |
| Programma | FP7-HEALTH
Specific Programme "Cooperation": Health |
| Code Call | FP7-HEALTH-2013-INNOVATION-1 |
| Funding Scheme | CP-IP |
| Anno di inizio | 2013 |
| Periodo (anno-mese-giorno) | 2013-10-01 - 2018-09-30 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
UNIVERSITA DEGLI STUDI DI FIRENZE
Organization address
address: Piazza San Marco 4 contact info |
IT (Florence) | coordinator | 866˙000.35 |
| 2 |
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
Organization address
address: 101 Rue de Tolbiac contact info |
FR (PARIS) | participant | 1˙758˙106.27 |
| 3 |
FONDAZIONE IRCCS ISTITUTO NEUROLOGICO CARLO BESTA
Organization address
address: VIA CELORIA 11 contact info |
IT (MILANO) | participant | 997˙421.60 |
| 4 |
UNIVERSITATSKLINIKUM ERLANGEN
Organization address
address: Maximiliansplatz 2 contact info |
DE (ERLANGEN) | participant | 899˙600.00 |
| 5 |
FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Organization address
address: VIA MOREGO 30 contact info |
IT (GENOVA) | participant | 897˙626.80 |
| 6 |
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
Organization address
address: Rue Michel -Ange 3 contact info |
FR (PARIS) | participant | 711˙847.60 |
| 7 |
THE UNIVERSITY OF LIVERPOOL
Organization address
address: Brownlow Hill, Foundation Building 765 contact info |
UK (LIVERPOOL) | participant | 597˙137.74 |
| 8 |
KING'S COLLEGE LONDON
Organization address
address: Strand contact info |
UK (LONDON) | participant | 500˙200.00 |
| 9 |
VARIONOSTIC GMBH
Organization address
address: SOFLINGER STRASSE 100 contact info |
DE (ULM) | participant | 498˙568.00 |
| 10 |
DI.V.A.L. TOSCANA SRL
Organization address
address: VIA MADONNA DEL PIANO 6 contact info |
IT (SESTO FIORENTINO FIRENZE) | participant | 448˙308.00 |
| 11 |
MICROMED S.P.A.
Organization address
address: VIA GIOTTO 2 contact info |
IT (MOGLIANO VENETO) | participant | 402˙000.00 |
| 12 |
UNIVERSITA DEGLI STUDI DI VERONA
Organization address
address: VIA DELL ARTIGLIERE 8 contact info |
IT (VERONA) | participant | 400˙389.59 |
| 13 |
UNIVERSITE LIBRE DE BRUXELLES
Organization address
address: Avenue Franklin Roosevelt 50 contact info |
BE (BRUXELLES) | participant | 336˙800.00 |
| 14 |
UNIVERSITY COLLEGE LONDON
Organization address
address: GOWER STREET contact info |
UK (LONDON) | participant | 300˙000.00 |
| 15 |
AMARNA THERAPEUTICS BV
Organization address
address: J H OORTWEG 21 contact info |
NL (LEIDEN) | participant | 299˙772.01 |
| 16 |
CEGAT GMBH
Organization address
address: PAUL EHRLICH STRASSE 17 contact info |
DE (TUBINGEN) | participant | 299˙087.40 |
| 17 |
CHRISTIAN-ALBRECHTS-UNIVERSITAET ZU KIEL
Organization address
address: OLSHAUSENSTRASSE 40 contact info |
DE (KIEL) | participant | 297˙780.00 |
| 18 |
CF CONSULTING FINANZIAMENTI UNIONE EUROPEA SRL
Organization address
address: Via Giuseppe Mussi 1 contact info |
IT (MILANO) | participant | 278˙068.03 |
| 19 |
AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Organization address
address: CALLE SERRANO 117 contact info |
ES (MADRID) | participant | 250˙305.98 |
| 20 |
KLINIKUM DER UNIVERSITAET ZU KOELN
Organization address
address: Kerpener Strasse 62 contact info |
DE (KOELN) | participant | 250˙000.00 |
| 21 |
CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Organization address
address: Chariteplatz 1 contact info |
DE (BERLIN) | participant | 249˙990.00 |
| 22 |
ISTITUTO GIANNINA GASLINI
Organization address
address: VIA GEROLAMO GASLINI 5 contact info |
IT (GENOVA) | participant | 192˙600.00 |
| 23 |
UNIVERSITA TA MALTA
Organization address
address: University Campus, Tal-Qroqq contact info |
MT (MSIDA) | participant | 121˙210.13 |
| 24 |
OSPEDALE PEDIATRICO BAMBINO GESU
Organization address
address: PIAZZA SAN ONOFRIO 4 contact info |
IT (ROMA) | participant | 95˙426.50 |
| 25 |
UNIVERSITA CATTOLICA DEL SACRO CUORE
Organization address
address: Largo Agostino Gemelli 1 contact info |
IT (MILANO) | participant | 47˙400.00 |
| 26 |
BAKER IDI HEART AND DIABETES INSTITUTE HOLDINGS LIMITED
Organization address
address: COMMERCIAL ROAD 75 VICTORIA contact info |
AU (MELBOURNE) | participant | 0.00 |
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Obiettivo del progetto (Objective)
'DESIRE will focus on epileptogenic developmental disorders EDD, i.e. early onset epilepsies whose origin is closely related to developmental brain processes. A major cause of EDD are malformations of cortical development (MCD), either macroscopic or subtle. EDD are often manifested as epileptic encephalopathies (EE), i.e. conditions in which epileptic activity itself may contribute to severe cognitive and behavioral impairments. EDD are the most frequent drug-resistant pediatric epilepsies carrying a lifelong perspective of disability and reduced quality of life. Although EDD collectively represent a major medical and socio-economic burden, their molecular diagnosis, pathogenic mechanisms (PM) and rationale treatment are poorly understood. Specific objectives of DESIRE are to advance the state of the art with respect to: (1) the genetic and epigenetic causes and PM of EDD, particularly epileptogenic MCD, to elucidate molecular networks and disrupted protein complexes and search for common bases for these apparently heterogeneous disorders. (2) the diagnostic tools (biomarkers) and protocols through the study of a unique and well-characterized cohort of children to provide standardized diagnosis for patient stratification and research across Europe. (3) treatment of EDD using randomized, multidisciplinary clinical protocols and testing preclinical strategies in experimental models to also address novel preventative strategies. The workplan spans from clinical observation, to whole exome studies, cellular and animal models and basic research, identification of biomarkers and improvement of diagnostic methods, and back to the clinical trials and assessment of innovative, targeted treatment strategies. The consortium partners have an outstanding track record in genetics, basic neurophysiology, neuropathology and clinical research. Specialized expertise will be made available by the SMEs involved to develop novel diagnostic tools for tailored treatment approaches.'
Introduzione (Teaser)
Early onset epilepsies impose a heavy social burden as well as a high economic cost on health care services. An EU project is investigating novel diagnostics and therapies.
Descrizione progetto (Article)
The DESIRE (Development and epilepsy - strategies for innovative research to improve diagnosis, prevention and treatment in children with difficult to treat epilepsy) project is focusing on epileptogenic developmental disorders (EDDs) which are early onset paediatric epilepsies related to developmental brain processes. The work is particularly significant as EDD is poorly understood and affected children often develop early drug resistance and cognitive decline.
DESIRE aims to elucidate the genetic and epigenetic causes and pathogenic mechanisms of EED to identify new biomarkers for diagnosis and prognosis, and to discover and improve therapies. A clinical trial is underway to determine if treating children with ketogenic diet prior to surgery for focal cortical dysplasia (malformation of the cortex) can improve prognosis.
So far, genomic research to find underlying causes has involved analysis of over 300 families with epilepsies. State of the art gene sequencing was performed as well as expression analysis and epigenomic profiling. New disease-causing genes and genetic variations were identified that could be linked to developmental malformations of the brain.
High-density autosomal maps of methylation sites allowed to identify novel epigenetic gene imprints. Use of sophisticated animal models pinpointed migration of neurons as an epileptogenic mechanism.
Neurophysiological biomarkers were explored using non-invasive diagnostic prototype tools that can analyse high frequency oscillations indicative of seizure onsets. Hardware and software needed for this novel diagnostic approach are pushed forward by the company partners in the project.
Since to date, pharma industry has treated the complex range of epilepsies as one disorder thereby largely ignoring diverse causes and diverse treatment needs of paediatric patients, DESIRE aims to explore at pre-clinical stage a battery of novel treatments, spanning from genetically modifying neurons to express new metabolites, and grafting inhibitory or silenced neurons, to employing nanoparticle carriers to drive therapeutic protein compounds across the Blood-Brain-Barrier to their brain targets, leading to attenuating or preventing seizure onset.
DESIRE adds a personalised therapy approach to epilepsy treatment in children, using the currently most advanced technologies. The project is based on a strong collaboration between the multidisciplinary research teams at hospitals and small and medium enterprises, to ensure the ambitious but very relevant objectives are met.
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