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FAITh SIGNED

Fighting Anxiety with Importin-based Therapeutics

Total Cost €

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EC-Contrib. €

0

Partnership

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 FAITh project word cloud

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

receptor    conduct    closely    leads    discovery    therapeutic    pilot    tests    axonal    mutant    sensing    agents    line    cell    synapse    discovered    burden    transport    initial    carry    society    diversity    drug    anxiolytic    repositioned    devise    signaling    phenotyping    deregulation    approved    fraught    stress    phenotype    compatible    roles    anxiolysis    synaptic    mechanisms    treatment    200    importin    screen    maximizing    either    validate    vivo    efficacy    protection    health    mouse    poc    potentially    analogs    date    size    commercialisation    avenues    behavioural    final    variety    molecular    functional    link    follow    anxiety    difficulty    compounds    regulation    additional    grant    structural    interesting    ip    neurotransmitter    importins    suboptimal    nucleus    course    disorders    identifications    hence    molecules    mutants    contexts    hts    drugs    rendering    injury    modern    assay    physiological    levels    limited    erc    dependent    presented    modulate   

Project "FAITh" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

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 Israel [IL]
 Total cost 150˙000 €
 EC max contribution 150˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-PoC
 Funding Scheme ERC-POC
 Starting year 2017
 Duration (year-month-day) from 2017-11-01   to  2019-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 150˙000.00

Map

 Project objective

Anxiety and stress-related conditions represent a significant health burden in modern society. Anxiety disorders are currently treated with a variety of agents targeting synaptic mechanisms. These agents either directly affect neurotransmitter receptor systems or modulate neurotransmitter levels or availability, but their long-term use is limited by problematic side effects and suboptimal efficacy. The development of new anxiolytic drugs has been fraught with difficulty, hence there is a need for new targets and new avenues for therapeutic development.

Importin-dependent transport mechanisms link synapse to nucleus in a diversity of physiological contexts, rendering them potentially interesting targets for behavioural control. However importins and related molecules have not been evaluated for roles in anxiolysis to date. We discovered the roles of importins in axonal injury signaling and in cell size sensing. During the course of our current ERC Advanced grant, and as part of one of the aims, we have conducted comprehensive phenotyping of importin mouse mutants to identify in vivo consequences of the deregulation of size control pathways. One importin mutant line presented a specific phenotype in anxiety tests, and follow-up analyses identified a new molecular pathway for anxiety regulation, and approved drugs affecting this pathway that can be repositioned for anxiety treatment.

In this PoC, we will (1) carry out IP protection on our initial identifications of anxiolytic drugs; (2) further validate the anxiolytic activities of these drugs and their closely related structural or functional analogs; and (3) devise an HTS-compatible assay for targeting the importin involved and conduct a pilot screen of ~200,000 compounds in this assay to identify new drug leads for anxiety treatment. As a final step, we will carry out (4) additional IP protection and pre-commercialisation tasks for maximizing the commercialisation potential of our discovery.

 Publications

year authors and title journal last update
List of publications.
2018 Nicolas Panayotis, Anton Sheinin, Shachar Y. Dagan, Michael M. Tsoory, Franziska Rother, Mayur Vadhvani, Anna Meshcheriakova, Sandip Koley, Letizia Marvaldi, Didi-Andreas Song, Eitan Reuveny, Britta J. Eickholt, Enno Hartmann, Michael Bader, Izhak Michaelevski, Mike Fainzilber
Importin α5 Regulates Anxiety through MeCP2 and Sphingosine Kinase 1
published pages: 3169-3179.e7, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.11.066
Cell Reports 25/11 2019-09-04

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