H2020Индивидуална стипендия2015–2018

INSCAPE · Imaging Voltage Gated Sodium Channels Using Positron Emission Tomography

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2015-05-15 → 2018-05-14
Финансиране от ЕС: 239 861 €
Участници: 2
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Нов метод за образяване изследва работата на натриевите канали в организма, например при сърцебиенето. Това помага за по-добрата диагностика на сърдечна недостатъчност, рак на гърдата и процеси в нервната система.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Imaging Voltage Gated Sodium Channels Using Positron Emission Tomography

In this project, we have developed a novel and unique imaging tool that helps visualizing pivotal physiological processes, which are important for human health, in vivo. In particular, our imaging technology allows extracting information on electrophysiological processes that underlie, for instance, heart beat in a non-invasive way. We believe that this is directly related to important societal challenges since cardiovascular disease is responsible for the majority of all deaths worldwide. Along these lines, we were able to demonstrate the translational potential of our invention for human heart failure, which is a live-threatening condition that currently lacks efficient diagnosis and treatment. Furthermore, we were able to elucidate an unexpected role of pain medication in a poorly understood part of the central nervous system. Finally, we made first steps in identifying additional potential of our new tool for impacting breast cancer diagnosis. Therefore, we can conclude that we have successfully achieve the overall objective of developing a novel translational imaging tool, which potentially improves patient outcomes. Noteworthy, the major indication fields of cardiovascular disease, pain, and cancer represent all-important and critical challenges of societies in Europe and worldwide. The overall educational objective was to provide training in chemical synthesis, small molecule analytics, radiochemistry, and molecular imaging to the researcher. These training goals were efficiently achieved by the mentorship and hands-on training at the partner institutions as well as attendance to educational workshops.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

KLINIKUM DER UNIVERSITAET ZU KOELN · KoelnКоординаторГермания
BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY · STANFORDСъединени щати