Origin of the Innov4-ePiK initiative

Since 2022, the GEEN-DS Chair is supported by the FAMA Fund hosted by the Swiss Philanthropy Foundation.

The Geen-DS program is a philanthropically funded chair that aims to deepen the understanding of the pathological mechanisms of Developmental and Epileptic Encephalopathies (DEEs) to accelerate and innovate in the development of therapies.

The GEEN-DS Chair is scientifically led at the Institut Imagine by Prof. Rima Nabbout within the Translational Research Team on Neurological Disorders co-directed by Dr. Edor Kabashi.

With more than 700,000 people in France affected, epilepsy is the neurological disease that affects the most people in Europe. In nearly 25% of cases, seizures are not the only manifestation of the disease. In some children, these seizures are accompanied by intellectual and cognitive deficiencies, behavioral problems and, in some cases, motor disorders. They may present a high risk of sudden and unexpected death. These rare and very disabling forms of epilepsy, named “Developmental and Epileptic Encephalopathies” (DEEs), are due to different types of etiologies, including genetic defects in the voltage-dependent channels, cellular structures that ensure the propagation of nerve signals in the brain.

“The treatment of these epilepsies with developmental disorders has so far been primarily empirical, relying on medications designed to treat seizures rather than addressing the underlying cause. The recent identification of these genetic forms paves the way for the development of targeted therapies. Placing the patient and their needs at the heart of these treatments and developing therapies based on an exploration of mechanisms using animal and cellular models are the main objectives of this chair.”

said Prof. Rima Nabbout & Dr. Edor Kabashi, project leads at the Institut Imagine.

This project aims to understand the molecular mechanisms of KCNB1-induced DEE by developing and combining state of the art cellular and animal models. These include neurons derived from iPSCs from patients, zebrafish knockout and knockdown models for the KCNB1 orthologue.

In this context, the Geen-DS Chair implements a scientific project based on four main pillars:

• Pillar 1: Integrating clinical data with advanced molecular analyses to enhance the understanding of the disease, identify patient groups with similar profiles, and highlight biomarkers.
• Pillar 2: Identifying deregulated pathways using patient-derived cellular models or specifically developed appropriate animal models.
• Pillar 3: Defining common pathological mechanisms in these models to identify and test new treatments.
• Pillar 4: Designing and testing new gene therapies, in combination with and alongside a pharmacological approach.

The successful funding of Innov4-ePiK is a great illustration of the virtuous leverage effect associated with the Chair scheme, has enabled the existing project to be developed further at a larger scale.