Edor Kabashi

Translational research for neurological disorders

Publish at 18.11.2019

Presentation

Edor Kabashi

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Neuronal excitability : From ALS to epilepsy

A major feature of ALS is an altered excitability of the motor circuit, a prevalent clinical hallmark in the diagnosis of this neurological disorder. Epilepsy is also characterized by the aberrant activation and excitability of neuronal circuits. Therefore, through an approach featuring molecular and physiological state of the art methodology, our team is seeking to define shared pathogenic mechanisms that lead to altered excitability in specific subsets of neurons related to these disorders.

Dr. Rima Nabbout, who leads the Reference Center for Rare Epilepsies (CReER) at Necker Hospital, is coordinating the epilepsy research project, bridging the clinical and fundamental aspects for an integrative approach. CReER is internationally renowned for the phenotypic classification of patients, the genetic analysis of large patient cohorts leading to the identification of novel genetic factors, and, in recent years, for spearheading successful clinical trials.

Translational approach for neuronal excitability disorders

Our team is involved in all the aspects of translational research in an integrative approach, from a better characterization of patients and their genetic markers, to modelling and fundamental research to identify appropriate therapeutic targets, and ultimately developing clinical trials to test novel treatments. This research is highly patient driven, with extensive phenotyping using the multidisciplinary expertise in clinical testing and the state-of-the-art platforms that are available at the Imagine Institute in the Necker Hospital site (e.g. genomic sequencing, electrophysiology, metabolic screening, imaging), while fostering collaborations with a network of national and international collaborations.

In order to identify novel genetic interactors, patient cohorts of epileptic conditions and ALS are being screened for disease-causing variants. We are developing cellular and animal models for these novel genetic variants to elucidate common pathophysiological signature occurring in disease. Using novel unbiased screening protocols we aim to identify pharmacological and genetic modifiers of pathological phenotypes. To accomplish this objective we rely on the power of zebrafish as a vertebrate model amenable to high-content phenotype-based screens. Factors that are neuroprotective in multiple animal and cellular models of disease will be fast-tracked to initial clinical trials. Through this approach we aim to be at the forefront of translational research for neurological disorders to advance therapeutic treatment for a range of these common neurological diseases.

Abstract 09

Research: a scientific adventure

Our goal: to better understand genetic diseases to better treat them.