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Treating Autism with a diuretic : interfering with neurodevelopment to understand and treat neurological and psychiatric diseases

on the October 19, 2017
11:30

Seminar by Yehezkel Ben-Ari (INMED, Marseille)

Developmental Disorders including Autism are triggered by intrauterine or delivery related insults. I have suggested that intrauterine genetic or environmental insults deviate developmental sequences of ionic currents leading to neurons with immature currents in adult brains. The presence in pathologies of neurons with excitatory GABA due to high (Cl-)I levels observed in immature neurons is an illustration of this Neuroarcheology concept (Ben-Ari TINS 2008). Thus, during delivery, oxytocin produces a powerful neuro-protective reduction of (Cl-)I levels (Tyzio et al Science 2006). This shift is abolished in 2 animal models of autism and its restoration by the diuretic NKCC1 chloride importer antagonist bumetanide attenuates the severity of autism in off springs (Tyzio et al Science 2014). We tested the effects of bumetanide first in a single site study (54 children, then in a double blind randomized multiple sites trial (87 children 2-18 years old) and observed positive results (Lemonnier et al, Transl. Psychiatry 2012 and 2017). We are now proceeding to a final EMA approved phase 3 clinical trial. We also showed that visual communication is ameliorated with the diuretic (Hadjikhani et al. Autism, 2016). Therefore, by restoring an efficient GABAergic inhibition, Bumetanide might provide a novel therapeutic perspective to treat developmental disorders (Ben-Ari TINS 2017). We suggest that the diuretic that exerts its actions on neurons endowed high (Cl-)I levels, attenuates perturbing behaviorally relevant oscillations thereby restoring harmonyin electrical activity. This approach is relevant to many other disorders as many ionic currents are also most likely affected by early insults. Studies are now centered on intrauterine and delivery alterations in autism and other developmental disorders.


Host: Michel Villaz. Yehezkel Ben-Ari will talk prior to the meeting on "Scientific Knowledge of Autism" scheduled to take place at the Université Grenoble-Alpes on 20 October.

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Serge Kampf amphitheatre
Updated on September 4, 2017

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