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FAITh SIGNED

Fighting Anxiety with Importin-based Therapeutics

Total Cost €

EC-Contrib. €

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 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.	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

List of publications.
year	authors and title	journal	last update
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 Î±5 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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