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INSCAPE TERMINATED

Imaging Voltage Gated Sodium Channels Using Positron Emission Tomography

Total Cost €

EC-Contrib. €

Partnership

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INSCAPE project word cloud

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

neuronal blockers 18 channels lifes benefits potentially rare pathogenesis drugs candidates block metabolic proteins voltage underlying tr tool tested positron hot carbon electrical isotopes vivo awaited imaging derivatives radioactive companies cns purpose btx global small secondly pharmacokinetics emission labeled implicated first tomography therapy fast rodent society gated valuable navs function 18f pain transmembrane pharmaceutical batrachotoxin stability 11c assays probe investigation primary pet neurodegenerative severe ing integral off nav half central fluorine emitting thirdly diseases link fluorescent employed disclosed therapies nav1 nervous communication neurons 11 signaling subsequently human isoforms scans monitoring peripheral revealing pns drug truncated intensely sodium synthesized completely

Project "INSCAPE" data sheet

The following table provides information about the project.

Coordinator	KLINIKUM DER UNIVERSITAET ZU KOELN Organization address address: Kerpener Strasse 62 city: KOELN postcode: 50937 website: www.uk-koeln.de 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	Germany [DE]
Total cost	239˙860 €
EC max contribution	239˙860 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2014
Funding Scheme	MSCA-IF-GF
Starting year	2015
Duration (year-month-day)	from 2015-05-15 to 2018-05-14

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	KLINIKUM DER UNIVERSITAET ZU KOELN KLINIKUM DER UNIVERSITAET ZU KOELN Organization address address: Kerpener Strasse 62 city: KOELN postcode: 50937 website: www.uk-koeln.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (KOELN)	coordinator	239˙860.00
2	BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY Organization address address: SERRA MALL 450 city: STANFORD postcode: 94305 2004 website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	US (STANFORD)	partner	0.00

Map

Project objective

Voltage gated sodium channels (NaVs) are the primary transmembrane proteins underlying fast electrical communication in neurons of the peripheral and central nervous system (PNS and CNS). Being such an integral part of neuronal signaling, they are implicated in a number of severe diseases that have a major impact on human society. However, drugs and established therapies targeting NaVs are rare due to common off-target effects. Therefore, new NaV-blockers will be developed and used for in vivo imaging using positron emission tomography (PET). For this purpose, novel derivatives of the recently disclosed truncated batrachotoxin (tr-BTX), which represent a completely new type of NaV-blockers, will be synthesized and their ability to block different NaV isoforms (NaV1.1 to 1.8) will be tested using fluorescent assays. The most promising candidates will then be labeled using different positron emitting isotopes such as carbon-11 (11C) and fluorine-18 (18F) exploiting different radioactive half-lifes and metabolic stability. The resulting “hot-tr-BTX” will be subsequently employed in small rodent PET-scans revealing their in vivo pharmacokinetics. This novel and unique tool will provide three major immediate benefits. First, hot-tr-BTX might deliver a general imaging probe for nervous activity in the PNS, and potentially the CNS, by monitoring NaV function in vivo. Secondly, this will allow the investigation of various pain conditions and neurodegenerative diseases and link their pathogenesis to NaV-function. Thirdly, the proposed research might deliver not only new NaV-blockers as potential drug candidates, but will also provide a valuable method facilitating the development of long awaited drugs targeting NaVs for pain therapy, a goal that is currently intensely investigated by numerous European and global pharmaceutical companies.

Publications

List of publications.
year	authors and title	journal	last update
2017	Matthias Schoenberger , Jacob Hooker , Martin Strebl , Al Schroeder , Timothy McKinsey , and Amrut Ambardekar Imaging cardiac voltage gated sodium channels using the novel F-18 radiotracer radiocaine published pages: , ISSN: , DOI:		2019-06-13
2017	Matthias Schoenberger, Frederick A. Schroeder, Michael S. Placzek, Randall L. Carter, Bruce R. Rosen, Jacob M. Hooker, Christin Y. Sander In Vivo [ 18 F]GE-179 Brain Signal Does Not Show NMDA-Specific Modulation with Drug Challenges in Rodents and Nonhuman Primates published pages: 298-305, ISSN: 1948-7193, DOI: 10.1021/acschemneuro.7b00327	ACS Chemical Neuroscience 9/2	2019-06-13

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