Descripción del proyecto
La amplificación dirigida de las especies reactivas del oxígeno podría combatir enfermedades graves
Una dieta rica en antioxidantes podría proteger contra varias patologías, desde el cáncer y los trastornos neurológicos hasta las enfermedades cardiovasculares. Los antioxidantes absorben radicales libres entre los que se encuentran las especies reactivas del oxígeno (ERO). Tal y como sugiere su nombre, las ERO son moléculas inestables cuyo contenido en oxígeno reacciona fácilmente con otras moléculas de la célula. Consideradas inicialmente agentes dañinos, ahora sabemos que también desempeñan una función básica en los procesos de las células sanas. La clave parece estar en la cantidad de tiempo que están presentes y en qué niveles en células concretas. NeutroCure está desarrollando formas de controlar las amplificaciones espacial y temporal de la generación de las ERO para tratar de manera efectiva patologías graves que se caracterizan por una disfunción en la homeostasis de las ERO.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Convocatoria de propuestas
Consulte otros proyectos de esta convocatoriaConvocatoria de subcontratación
H2020-FETOPEN-2018-2019-2020-01
Régimen de financiación
RIA - Research and Innovation actionCoordinador
91054 Erlangen
Alemania