Neurodegenerative diseases (ND) represent a major healthcare problem worldwide and in Europe with its ageing population. ND affect mostly adults and can last for decades, causing long term suffering to patients and their families. There are more than 600 different ND, affecting millions of people. European health services spent approximately 72 billion € for ND treatments in year 2006. Currently, 16% of the European population is over 65, and this figure is expected to reach 25% by 2030. As the proportion of elderly people is increasing, these costs are becoming a real burden to the society.
Current treatments for ND are mostly palliative or only treat the symptoms rather than the cause, hence provide only slight relief instead of cure. Over the years our understanding of the biological basis of ND has increased, and numerous pathological mediators of ND have been identified.
Although the initiating factors of ND can vary greatly, a sustained inflammatory response is a critical mechanism responsible for the progressive nature of neurodegeneration. Neuroinflammatory patterns are described in numerous neuroinflammatory disorders like multiple Sclerosis (MS), amyotrophic lateral sclerosis (ALS), some forms of epilepsies associated with cell loss like mesiotemporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) and other rare autoimmune peripheral neuropathies (APL).
Neuroinflammation is also observed in more frequent ND, such as Alzheimer disease (AD), Parkinson disease (PD). Recently, a key role of reactive oxygen species (ROS) generated by NADPH oxidases (NOX) in neuroinflammation-mediated brain dysfunction has been discovered. Built on this discovery, the global aim of NEURINOX is to develop novel therapeutic targets for the treatment of inflammatory ND focusing on NOX enzymes representing a powerful target for the development of therapies against ND.
The specific ND this project will be targeting include ALS, MS, MTLE-HS and APN, while the applications of the anticipated findings are expected to have an even broader impact.
Main NEURINOX research activities include studies of NOX activity in animal models and in human patient samples, the development and validation of the effect of NOX regulating drugs (small molecules) in animal models and a phase I-II clinical trial with a NOX regulating drug to determine safety and efficacy on a small population of ALS patients.
This 5 years research work should provide the following main results:
- A better understanding of common mechanisms of brain diseases, and in particular oxidative stress-mediated ND and the link between the different NOX isoforms and neuroinflammation and how their activities control the neuroinflammatory process in ND.
- Novel molecular pathways, genes and SNPs and biomarkers of oxidation correlating with NOX activity, neuroinflammation and ND progression.
- Small molecules validated in NEURINOX using animal models of ND.
Validation of NOX as viable targets for the development of therapeutics for ALS and potentially many other neuroinflammatory ND.
The NEURINOX project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n°278611