Olivier David: Probing the Brain to Discover the Drugs of Tomorrow

Olivier David is the head of research at the Grenoble Institute of Neurosciences (GIN). As part of the Brain Stimulation and Systems Neuroscience team, he works to describe the physiopathological mechanisms associated with nerve cells in some neurological and psychiatric illnesses. For several years, he has been focusing on characterizing the neural networks in the cortex of epileptic patients, on the basis of cortical stimulations. Even though this colossal task has already resulted in the establishment of an atlas of all of these networks, David is undertaking a new stage that, in the long run, will facilitate drug development.

What is the objective of the EXCITATOR project for which you received a European Research Council (ERC) Proof of Concept Grant?

While the purpose of most Proof of Concept Grants (POC) is to confirm experimental results in a clinical setting, the EXCITATOR project differs in that it goes in the opposite direction. Our idea is to transfer a methodology that we developed for studying the neural electrical activity of epileptic patients to preclinical conditions. The goal is to have an innovative approach in small animals, making it possible to optimize the evaluation of experimental drugs that target the nervous system. This animal model will allow SynapCell, a Grenoble-based company that emerged from the University in 2005, to draw on our research and make use of our conclusions for pharmaceutical development purposes.

In concrete terms, which technique does this approach rest upon?

The idea is to deliver electrical microstimulation using intracerebral electrodes, and to use electroencephalography (EEG) to study the electric signal moving through the cerebral areas studied in response to this stimulation. This will determine the excitability and connectivity of the regions stimulated and recorded.

In the context of my previous project – F-TRACT, which was also awarded a European grant in 2013 (the ERC Consolidator Grant) – we developed an atlas of the cortical connections based on the data obtained from epileptic patients who were candidates for surgery. The POC grant will allow us to apply this major methodological undertaking in order to discover new compounds. In the long run, this could indeed be adapted to evaluate, in vivo, changes in cerebral activity induced by a drug targeting the central nervous system, such as an antiepileptic or a drug designed to treat Alzheimer’s disease.

To what degree will this grant allow you to reach your objective more easily?

The grant, of €150,000 for one year, will be used to set up an experimental and industrial plan that will allow us to validate our model and ensure it is sensitive enough to be used in the preclinical evaluation of central nervous system drugs. In concrete terms, it will mainly allow us to spend time on a market study and to make our scientific developments compatible with industrial use by Synapcell.

This will open up new horizons for the team that will be involved in F-TRACT into 2019. Without the European grant received for this project in 2013 (€2 million), it would not have been possible to build a team large enough to establish our atlas as quickly and robustly as we did. In particular, the grant made it possible for us to work on another scale by compiling the data, not of two or three hundred French patients, but of nearly 1,500 patients at the international level. It is obvious that the POC grant will also facilitate the exploration of F-TRACT’s transfer potential.

 

Find out more about Olivier David and his work

Olivier David leads the Brain Stimulation and Systems Neuroscience team at the Grenoble Institute of Neurosciences (Inserm unit 1216/Université de Grenoble Alpes).