NeuroDeRisk is an “Innovative Medicines Initiative” (IMI2) project aiming to provide novel validated integrated tools for improving the preclinical prediction of adverse effects of pharmaceuticals on the nervous system and thus help to de-risk drug candidates earlier in the Research and Development phases.
The adverse effects of pharmaceuticals on the central or peripheral nervous systems are poorly predicted by the current in vitro and in vivo preclinical studies performed during Research and Development (R&D) process. Therefore, increasing the predictivity of the preclinical toolbox is a clear need, and would benefit to human volunteers/patients (safer drugs) and Pharmaceutical Industry (reduced attrition). By combining top level scientists in neurobiology/toxicology with successful software developers, the NeuroDeRisk Consortium will aim at tackling three of the most challenging adverse effects: seizures, psychological/psychiatric changes, and peripheral neuropathies.
Our approach is a global one, and it started with an in-depth evaluation of knowledge on mechanisms of neurotoxicity (biological pathways as well as chemical structures and descriptors, using in particular historical data). Then searched for innovative tools, assays and studies covering in silico, in vitro and in vivo approaches. This includes in particular:
- a molecular design platform,
- use of human induced pluripotent stem cells,
- establishing new blood-brain-barrier models,
- pharmacokinetics
- immunohistochemistry,
- transcriptomics,
- RNA editing biomarkers,
- video-monitoring and
- Non-invasive in vivo technologies (ultra high resolution video-monitoring, telemetry, actimetry)
The last step aims at combining these tools in an integrated platform for improved risk-assessment and decision-points throughout R&D process, providing the prediction of adverse effects by drug candidates based on potential neurotoxicity.
Thus, we deliver increased knowledge on mechanisms of nervous system modulation and toxicity, as well as a better understanding of molecular interaction factors that favor neurotoxicity risks for drug candidates.
All the results feed into an integrated risk assessment approach for providing better decision points throughout the preclinical drug discovery process.
The NeuroDeRisk consortium positively impacts IMI2 KPI 2 and 3, Regulation Objective b6 "improve the current drug development process by providing the support for the development of tools, standards and approaches to assess efficacy, safety and quality of regulated health products”.
By investigating the molecular basis of drugs and/or drug candidate related adverse outcomes on the central and peripheral nervous system, the consortium lays the ground work for the development of better and safer drugs. By providing information on new biomarkers related to such adverse outcomes, and making available software tools for prediction of off-target interactions, the consortium contributes to replacement, reduction, and refinement of animal experiments (i.e. the 3R paradigm).
