Nox enzymes as mediators of inflammation-triggered neurodegeneration: modulating nox enzymes as novel therapies

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Project Title: Nox enzymes as mediators of inflammation-triggered neurodegeneration: modulating nox enzymes as novel therapies
Project Number: CORDIS-102532
Project web address: Follow on CORDIS
Organization: Universite De Geneve, Switzerland, Geneve
Collaborators: University Of Sydney, AU
University Of Zurich, CH
Karolinska Institutet, SE
Università Degli Studi Di Torino, IT
Universite Joseph Fourier - Grenoble 1, FR
Arttic, FR
Redoxis Ab, SE
Ethniko Kai Kapodistriako Panepistimio Athinon, GR
Biomedical Research Foundation, Academy Of Athens, GR
Victor Chang Cardiac Research Institute Limited Lbg, AU
Universite Grenoble Alpes, FR
Neurix Sa, CH
Genkyotex Innovation Sas, FR
Synapcell Sas, FR
Principal Investigators (PI): Adriano Aguzzi, CH
Eric Papon, FR
Jill Blomstrand, SE
Dimitris Raptis, GR
Donatella Amadori, IT
Peter Olofsson, SE
Efstathia Kafentzi, GR
Sophie Beaubron, FR
Karl-Heinz Krause, CH
Kate Taylor, AU
Samuel Constant, CH
Rebecca Margarito, FR
Kiran Narsey, AU
Yann Roche, FR
 
Project Description:
NEURINOX aims at elucidating the role of NADPH oxidases (NOX) in neuroinflammation and its progression to neurodegenerative diseases (ND), as well as evaluating the potential of novel ND therapeutics approaches targeting NOX activity. NOX generate reactive oxygen species (ROS) and have emerged as regulators of neuroinflammation. Their role is complex: ROS generated by NOX lead to tissue damage in microglia-mediated neuroinflammation, as seen in amyotrophic lateral sclerosis (ALS), while absence of ROS generation enhances the severity of autoimmune-mediated neuroinflammation, as seen for e.g. in multiple sclerosis (MS).The objective of the 5 years NEURINOX project is to understand how NOX controls neuroinflammation, identify novel molecular pathways and oxidative biomarkers involved in NOX-dependent neuroinflammation, and develop specific therapies based on NOX modulation. The scientific approach will be to: (i) identify NOX-dependent molecular mechanisms using dedicated ND animal models (ii) develop therapeutic small molecules either inhibiting or activating NOX and test their effects in animal models (iii) test the validity of identified molecular pathways in clinical studies in ALS and MS patients.NEURINOX will contribute to better understand brain dysfunction, and more particularly the link between neuroinflammation and ND and to identify new therapeutic targets for ND. A successful demonstration of the benefits of NOX modulating drugs in ALS and MS animal models, and in ALS early clinical trials will validate a novel high potential therapeutics target for ALS and also many types of ND. NEURINOX has hence a strong potential for more efficient ND healthcare for patients and thus for reducing ND healthcare costs.This multi-disciplinary consortium includes leading scientists in NOX research, ROS biology, drug development SMEs, experts in the neuroinflammatory aspects of ND, genomics and proteomics, and clinicians able to translate the basic science to the patient.
 
Project Terms:
life sciences