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Development of “smart” amplifiers of reactive oxygen species specific to aberrant polymorphonuclear neutrophils for treatment of inflammatory and autoimmune diseases, cancer and myeloablation.

Projektbeschreibung

Gezielte Vermehrung reaktiver Sauerstoffspezies im Kampf gegen schwere Krankheiten

Eine antioxidantienreiche Ernährung kann verschiedensten Krankheiten vorbeugen, von Krebs über neurologische bis hin zu Herz-Kreislauf-Erkrankungen. Antioxidantien neutralisieren freie Radikale, u. a. reaktive Sauerstoffspezies (ROS). Reaktive Sauerstoffspezies sind instabile Moleküle, die Sauerstoff transportieren und leicht mit anderen zellinternen Molekülen reagieren. Obwohl sie zunächst als schädlich galten, weiß man inzwischen auch um ihre wichtige physiologische Funktion in Zellen. Der wichtigste Faktor ist dabei offenbar, wie lange und in welcher Konzentration sie in der Zelle verbleiben. So entwickelt das Projekt NeutroCure Methoden, um die räumliche und zeitliche Vermehrung von reaktiven Sauerstoffspezies steuern und so schwere Krankheiten behandeln zu können, die auf eine gestörte Homöostase der reaktiven Sauerstoffspezies zurückgehen.

Ziel

Reactive oxygen species (ROS) have key functions in healthy organism such as redox signaling for regulation of cell growth, triggering formation of neutrophil extracellular traps (NETs), and modulation of inflammation. Since in high concentration ROS are damaging to tissues, nature has evolved precise mechanisms to control their generation at the required time, concentration and space, proximal to their target. Disturbance of these mechanisms leads to aberrant ROS production that causes uncontrolled inflammation, occurs in myeloablation caused by radio- or chemotherapy and is a crucial feature of cancer cell phenotype as well as autoimmunity. Despite the damaging properties of ROS it is a paradox that pharmaceutical ROS amplifiers can reverse (“cure”) many pathologic features. For example, ROS-induced cancer cell killing inhibits cancer growth, ROS-induced deactivation of T-cells and NETs generation contributes to resolution of inflammation, and ROS-induced boosting of haematopoiesis can relieve myeloablation. These exciting possibilities have not been realized in clinical settings yet, since the high level of temporal and spatial control of ROS generation, required to allow for safe patient treatment, has yet not been achieved for any known drug. NeutroCure will be the first attempt to achieve a breakthrough solution to this problem. Using an innovative approach based on the multiple-trigger prodrug activation, this consortium will develop safe ROS amplifiers capable of boosting ROS specifically in abnormal polymorphonuclear neutrophils associated with cancer, uncontrolled inflammation and relevant for myeloablation without affecting normal cells. NeutroCure consists of 6 European academic partners and an SME who will promote commercialization of the new drugs. We expect that this project will have a great positive impact on the Society by providing previously unexplored treatment solutions for severe pathological conditions caused by dysregulated ROS-production.

Aufforderung zur Vorschlagseinreichung

H2020-FETOPEN-2018-2020

Andere Projekte für diesen Aufruf anzeigen

Unterauftrag

H2020-FETOPEN-2018-2019-2020-01

Koordinator

FRIEDRICH-ALEXANDER-UNIVERSITAET ERLANGEN-NUERNBERG
Netto-EU-Beitrag
€ 629 000,00
Adresse
SCHLOSSPLATZ 4
91054 Erlangen
Deutschland

Auf der Karte ansehen

Region
Bayern Mittelfranken Erlangen, Kreisfreie Stadt
Aktivitätstyp
Higher or Secondary Education Establishments
Links
Gesamtkosten
€ 629 000,00

Beteiligte (11)