Cellular Model for the evaluation of drug candidates against Alzheimer's disease
One of the obstacles to the discovery of effective drugs for Alzheimer's disease (AD) is the lack of models perfectly mimicking the disease.
Current models which are based on in silico tests or the use of transgenic animals are not very effective for evaluating drug candidates. We are looking to set up approaches combining the use of cellular tools and a pharmacological agent capable of inducing a selective production of Aß-42 peptide (considered one of the most toxic species of Aß peptides), the phosphorylation of the Tau protein and the reduction of the "synaptophysin", involved in the synaptic connections. Using this model allows to assess molecules collections of daily exposure, natural or anthropogenic, capable of acting as exogenous factors that contribute to the development of AD. This project, jointly being conducted by various academic institutions and industrial partners, was initiated with the FUI (Fonds Unique Interministériel).
Physiology of the blood-brain barrier during cerebral development and targeting of drug candidates
To complete its limited and selective permeability, the blood-brain barrier has, in addition to its physical structure, specialized membrane transporters (influx and efflux) that play a key role in the pharmacokinetics and pharmacological activity of many drugs. We aim to understand how the activity of these transporters is regulated during brain development and in the context of neuroinflammation (ANRS Program), to optimize the entry of drugs into the central nervous system. Thus, we are involved in a research program (the Lejeune Foundation) to improve the release in the brain of creatine derivatives for the treatment of a rare brain metabolic disease associated with creatine transporter deficiency. This project is conducted in partnership with another team from the institute (IBITECS/SCBM) and with the INSERM U393 unit of the Necker Hospital, Pr Pascale De Lonlay. Finally, we are involved in a peptide and macromolecule vectorization project funded under a FP7-TRANS-INT European program. This project involves various European academic institutions and industrials (Sanofi-Aventis, Roche Diagnostic...).
Neurotoxicology
The objectives of this research program are:
- Compare and characterize the brain penetration and neurotoxicity profile of drug candidates and nanoparticles (NanoTrans, DIMSent Programs)
- Identify molecular signatures characterizing neurotoxicity mechanisms for these molecules;
- Ultimately develop integrated models of neurotoxicity.