Imaging Voltage Gated Sodium Channels Using Positron Emission Tomography

Projektinformationen

INSCAPE

ID Finanzhilfevereinbarung: 656644

DOI 10.3030/656644

Das Projekt endete am 5 Mai 2018

EK-Unterschriftsdatum 23 April 2015

Startdatum 15 Mai 2015

Enddatum 14 Mai 2018

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten € 239 860,80

EU-Beitrag € 239 860,80

Koordiniert durch

KLINIKUM DER UNIVERSITAET ZU KOELN
Germany

Ziel

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.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › neurobiology
• medical and health sciences › basic medicine › pharmacology and pharmacy › drug discovery
• natural sciences › chemical sciences › inorganic chemistry › alkali metals
• natural sciences › biological sciences › biochemistry › biomolecules › proteins
• medical and health sciences › basic medicine › pharmacology and pharmacy › pharmacokinetics

Schlüsselbegriffe

• Voltage Gated Sodium Channels
• Pain Research
• Neurodegeneratie Diseases
• Modified Natural Products
• Medicinal Chemistry
• Positron Emission Tomography

Programm/Programme

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility

Thema/Themen

• MSCA-IF-2014-GF - Marie Skłodowska-Curie Individual Fellowships (IF-GF)

Aufforderung zur Vorschlagseinreichung

H2020-MSCA-IF-2014

Finanzierungsplan

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Koordinator

KLINIKUM DER UNIVERSITAET ZU KOELN

• Netto-EU-Beitrag: € 239 860,80
• Adresse: Kerpener Strasse 62 ; 50937 Koeln ; Deutschland
• Region: Nordrhein-Westfalen › Köln › Köln, Kreisfreie Stadt
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 239 860,80

Partner (1)

Partner

Partnerorganisationen tragen zur Umsetzung der Aktion bei, unterzeichnen jedoch nicht die Finanzhilfevereinbarung.

BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

Vereinigte Staaten

• Netto-EU-Beitrag: € 0,00
• Adresse: SERRA MALL 450 ; 94305 2004 Stanford
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 160 130,40