CE17 - Recherche translationnelle en santé

Characterization of placental biomarkers of fetal brain defects after in utero alcohol exposure – AlcoBrain

Submission summary

Alcohol consumption during pregnancy constitutes the main cause of acquired handicap and most children presenting fetal alcohol spectrum disorders (FASD) are not diagnosed at birth. However, these infants are not devoid of neurodevelopmental troubles that will be detected at school-age. Neonatal diagnosis of FASD would allow saving precious years of care at ages where brain plasticity is maximal. The AlcoBrain program is focused on the identification of placental biomarkers of brain vascular defects. The program recently led to the deposit of two patents associating the Rouen Hospital, the Rouen University and Inserm transfert. These patents concern the validation of a functional “Placenta/Brain” axis and the identification of PlGF as a first biomarker of fetal brain angiogenesis impairments. The research project is developed using preclinical and clinical approaches and associates 4 partners (2 clinical departments from Charles Nicolle (Rouen) and Robert Debré (Paris) hospitals, and 2 Inserm units). The project proposed for funding by the ANR 2018 call is focused on the characterization of the neurodevelopmental consequences of the cortical angiogenic impairments demonstrated in both animals and alcohol-exposed infants. The project is structured in 3 work-packages in order to investigate i) the impact of placental/PlGF dysfunction on the migration/positioning of 2 nervous populations (GABA interneurons and oligodendrocytes), ii) the impact of alcohol on the secretory function of the human placenta in the fetal circulation by targeting angiogenic factors and iii) the correlation between PlGF levels in the placenta/umbilical blood at birth and the follow-up of age-related neurodevelopmental deficits. The AlcoBrain program is performed using both pre-clinical approaches (gene repression/over-expression strategies in transgenic mice) and clinical studies (human placenta perfusion experiments and an already engaged clinical protocol). The project aims to validate the biomarker value of PlGF at birth to identify infants with risk of neurodevelopmental deficits at school-age allowing the early diagnosis of FASD (FR1555727 – PCT/EP2016; FR1661813).

Project coordination

Bruno GONZALEZ (Genomics and Personalized Medicine in Cancer and Neurological Disorders)

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.

Partner

Inserm U1245 - Rouen University Genomics and Personalized Medicine in Cancer and Neurological Disorders
Service de Pédiatrie Néonatale et Réanimation - Robert Debré Hospital Paris
Service de Pédiatrie Néonatale et Réanimation - CHU Rouen
UPDescartes - UMR-S 1139 PHYSIOPATHOLOGIE & PHARMACOTOXICOLOGIE PLACENTAIRE HUMAINE

Help of the ANR 376,689 euros
Beginning and duration of the scientific project: November 2018 - 36 Months

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