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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.

Project description

Targeted amplification of reactive oxygen species could fight serious diseases

A diet rich in antioxidants could protect against a variety of pathologies from cancer and neurological disorders to cardiovascular disease. Antioxidants soak up free radicals among which are reactive oxygen species (ROS). ROS, as their name suggests, are unstable molecules containing oxygen that easily react with other molecules in a cell. Initially considered damaging agents, we now know they also play a key role in healthy cell processes. The key seems to be in the amount of time they are present and at what levels in specific cells. NeutroCure is developing ways to control the spatial and temporal amplification of ROS generation to effectively treat severe pathological conditions characterised by a dysfunction in ROS homeostasis.

Objective

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.

Call for proposal

H2020-FETOPEN-2018-2020

See other projects for this call

Sub call

H2020-FETOPEN-2018-2019-2020-01

Coordinator

FRIEDRICH-ALEXANDER-UNIVERSITAET ERLANGEN-NUERNBERG
Net EU contribution
€ 629 000,00
Address
SCHLOSSPLATZ 4
91054 Erlangen
Germany

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Region
Bayern Mittelfranken Erlangen, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 629 000,00

Participants (11)