Autism is a complex neurodevelopmental disorder that affects about one in 100 children, with a prevalence four times higher in boys. The causes of this disorder remain unknown to date and no drug therapy is available. Treatment is only symptomatic and requires personalized educational therapies.
We have been working for several years on the mechanism of action of bumetanide. By 2014, our work, published in Science, showed that it was possible, in animal models, by treating pregnant females with bumetanide, to prevent autistic behavior in their offspring. Bumetanide affects the high concentrations of chloride in neurons noticed in some neurodevelopmental diseases such as autism. This work quickly open the road to clinical studies in humans. A Phase 2A study was initially conducted by Dr. E. Lemonnier, and a multi-center Phase 2B trial was conducted by Neurochlore in 6 centers in France on nearly 90 children (2-18 years). This study has shown encouraging results in favor of bumetanide on several scales of autism. These results, published recently, make it possible to consider a global management of the disorder and particularly its key symptoms, the social deficit and the stereotyped behaviors. Prolonged use of bumetanide in children can be considered calmly because its acceptability in adults is well documented, this product being used in heart failure and renal and hepatic oedema for many years.
After a partnership agreement between Neurochlore and Servier Laboratories, the third and final stage of this long-term clinical trial is expected to begin soon. Phase 3 will continue for another year on approximately 300 children aged 2 to 18 years under strictly ethical conditions, the protocol having just been approved by the European Medicines Agency (EMA). An application for a Marketing Authorization is considered at the end of 2021.
“I am delighted to see that the fundamental research we have been carrying out for several decades on the development of ionic currents will lead to the treatment of a syndrome that does not have any at the present time. This illustrates the importance of basic cognitive research and collaboration with physicians and psychiatrists such as Dr. E. Lemonnier. I have always considered that experimental research must be centered on major concepts without hoping for an application that may (unexpectedly) occur later on. Understanding the development of neural networks in pathological conditions opens the way to new therapeutic approaches to cerebral diseases, especially in the case of syndromes having an intrauterine origin”. Yehezkel Ben-Ari