Bumetanide to treat autism spectrum disorders: Clinical observations

In a wide range of brain disorders, experimental observations suggest a rise of intracellular chloride levels leading to a loss of the GABAergic inhibitory drive and even a polarity shift with GABA exerting excitatory actions. These observations suggest that drugs capable of restoring the inhibitory drive of GABA might be useful in a clinical perspective. Here, we summarize our studies aimed at testing the efficacy of the NKCC1 chloride importer inhibitor Bumetanide that restores GABAergic inhibition to treat children and adolescents with Autism Spectrum Disorders (ASD). We have successfully performed two phase II trials in France and are now sponsoring an international phase III study with 400 children and adolescents between 2 and 18-years-old. We also summarize brain imaging studies showing that Bumetanide reduces amygdala activation produced by constraint eye contact. Collectively, these promising results validate the usefulness of this agent to treat ASD.