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Advanced Studies towards Knowledge on Lyssavirus Encephalitis
Pathogenesis Improving Options for Survival

Objective

The overall aim of ASKLEPIOS is to unravel and increase our understanding of the mechanisms that govern pathogenesis of rabies virus (RABV) infection, in pursuit of the rational identification of novel therapeutic leads for rabies encephalitis. Several studies have been conducted over the past decades attempting to unravel the pathogenesis of this deadly disease, however with limited success. New knowledge on the mechanisms of the RABV life-cycle and interaction with the host is needed to identifying clinically applicable therapeutic leads, in search of rational intervention strategies. The project objectives are to:
1. Identify molecules that inhibit RABV replication
2. Identify molecules that inhibit detrimental host responses to RABV infection:
3. Show whether opening the blood-brain-barrier (BBB) improves treatment efficacy:
4. Validate the potential of the molecules identified under 1 and 2 to be used as post-exposure prophylaxis (PEP) when classical PEP is ineffective.
In pursuit of these objectives ASKLEPIOS will perform in vitro screening of the anti-viral effect of type-I IFNs, MAP kinase inhibitors and siRNAs. Second, the therapeutic potential of inhibiting the pyroptotic pathway and inflammatory response will be investigated by using inhibitors of caspase-1, IL-1β, TNF-α IL-6 and MAP kinases. Third, the capacity of molecules to reach the brain will be first evaluated using an efficient in vitro BBB system and in vivo mouse studies.. The most efficient molecule to open the BBB will be co-administrated with the selected therapeutic molecules in the subsequent stages of the project. The results will be collected and synthesized and tested in mice to identify the most effective approach. The ability to clear infection and recover from rabies will be evaluated for each therapeutic scheme identified

Call for proposal

FP7-HEALTH-2013-INNOVATION-1
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Coordinator

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Address
Dr Molewaterplein 40
3015 GD Rotterdam
Netherlands

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Paul Huber (Mr.)
EU contribution
€ 706 679

Participants (9)

Food and Environment Research Agency
United Kingdom
EU contribution
€ 470 057
Address
Area 1a, Nobel House, Smith Square 17
SW1P 3JR London

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Clare French (Mrs.)
VYZKUMNY USTAV VETERINARNIHO LEKARSTVI
Czechia
EU contribution
€ 482 506
Address
Hudcova 296/70
621 00 Brno

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Activity type
Other
Administrative Contact
Daniel Ruzek (Dr.)
PANSTWOWY INSTYTUT WETERYNARYJNY - PANSTWOWY INSTYTUT BADAWCZY
Poland
EU contribution
€ 428 299
Address
Partyzantow 57
24100 Pulawy

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Activity type
Research Organisations
Administrative Contact
Jan Zmudzinski (Prof.)
SZENT ISTVAN EGYETEM

Participation ended

Hungary
EU contribution
€ 175 459,20
Address
Pater Karoly Utca 1
2100 Godollo

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Tamas Bakonyi (Dr.)
AGRARTUDOMANYI KUTATOKOZPONT
Hungary
EU contribution
€ 239 940
Address
Brunszvik Street 2
2462 Martonvasar

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Activity type
Research Organisations
Administrative Contact
Miklós Gyuranecz (Dr.)
KATHOLIEKE UNIVERSITEIT LEUVEN
Belgium
EU contribution
€ 59 040
Address
Oude Markt 13
3000 Leuven

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Myriam Witvrouw (Dr.)
ARTEMIS BIO-SUPPORT B.V.
Netherlands
EU contribution
€ 347 360
Address
Molengraaffsingel 10
2629 JD Delft

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Eric Claassen (Prof.)
INSTITUT PASTEUR
France
EU contribution
€ 21 000
Address
Rue Du Docteur Roux 25-28
75724 Paris Cedex 15

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Activity type
Research Organisations
Administrative Contact
Thomas Wiest (Mr.)
ALLATORVOSTUDOMANYI EGYETEM
Hungary
EU contribution
€ 64 540,80
Address
Istvan Utca 2
1078 Budapest

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Tamás Bakonyi (Prof.)