Development of “smart” amplifiers of reactive oxygen species specific to aberrant polymorphonuclear neutrophils for treatment of inflammatory and autoimmune diseases, cancer and myeloablation.
Description: 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.
Funder: European Commission
Amount: €3,000,000
Funding type: research
Funder scheme: H2020 - RIA
Start date: 2020-01-01
End date: 2025-10-31
Institution: FRIEDRICH-ALEXANDER-UNIVERSITAET ERLANGEN-NUERNBERG
Funded outputs count: 68
Funder award ID: 861878
OpenAlex ID: G1357743905