Welcome to the NeuroDeRisk Project
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 focus is on three major types of neurotoxicity:
SZ – Tox
convulsant & seizure-inducing effects
P/P – Tox
psychological & psychiatric side effects
PNS – Tox
peripheral nervous system toxicity
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, starting 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), followed by the development of innovative tools, assays, and studies covering in silico, in vitro and in vivo approaches. This includes in particular:
- a molecular design platform,
- artificial intelligence,
- human induced pluripotent stem cells,
- blood-brain-barrier models,
- RNA editing biomarkers,
- video-monitoring and
- Nnon-invasive in vivo technologies (ultra high resolution video-monitoring, telemetry, actimetry)
The final step of our project aims at combining these tools in an integrated platform for improved risk-assessment and decision-points throughout the R&D process, providing a prediction platform for de-risking drug candidates based on potential neurotoxicity.
- Open Access Article: Inhibition of GABAA receptors by antipsychotics and antidepressantsMany psychotherapeutic drugs, including clozapine, display polypharmacology and act on GABAA receptors. Patients with schizophrenia show alterations in function, structure and molecular composition of the hippocampus, and a recent study demonstrated aberrant levels of hippocampal α5 subunit-containing GABAA receptors.
- 30-months status of the project and of each work package online meetingIt was time again for a “Status of the Project” meeting. This time the consortium partners came together because we have been working on our objectives for 30 months. In order to enable our colleagues from overseas to participate, the online conference took place in the afternoon.