CE17 - Recherche translationnelle en santé

Developmental Mechanisms of Epilepsy and Cognitive Deficits in STXBP1-Related Childhood Encephalopathies – SYNDEV

Submission summary

This translational project aims to identify the developmental mechanisms and biomarkers of cognitive impairment and epilepsy associated with mutations of the gene syntaxin-binding-protein 1 (STXBP1). STXBP1 haploinsufficiency is one of the prevalent causes of developmental neurological disorders, including early onset epileptic encephalopathies. Most patients have severe to profound intellectual deficits with little correlation between seizure onset or severity, and the degree of cognitive impairment. While STXBP1-encephalopathies (STXBP1-E) have been previously studied in patients and in animal models, no study so far has focused on the developmental impact of STXBP1 haploinsufficiency on brain maturation.
Here, we aim to 1) understand the natural history of STXBP1-Es through electrophysiological and behavioral assessments in patients and in an animal model; 2) determine if there is a critical period of vulnerability to STXBP1 mutations in terms of epilepsy and neurological development, and 3) analyze the downstream electrophysiological consequence of STXBP1 haploinsufficiency at the cellular and network levels.
This project will use a combination of in-vivo and in-vitro electrophysiological techniques in patients and animal models. While we already have a knock-out mouse model of STXBP1-E in our laboratory, we will develop a reversible model, allowing us to restrict haploinsufficiency to specific developmental periods. Ultimately our results will help tailoring better treatment strategies for STXBP1-E and the family of neurodevelopmental disorders it belongs to. This project is translational in nature since it involves in each of its research axes, the comparison of clinical and experimental data in patients and animal models during early development.

Project coordinator

Monsieur Pierre-Pascal LENCK-SANTINI (Institut de Neurobiologie de la Méditerranée)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


INMED Institut de Neurobiologie de la Méditerranée
INMED Institut de Neurobiologie de la Méditerranée
DRS-APHM Assistance Publique - Hôpitaux de Marseille

Help of the ANR 701,782 euros
Beginning and duration of the scientific project: December 2022 - 48 Months

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