Using bumetanide to treat autism appears promising but further clinical trials are needed to confirm this approach

In spite of its high incidence, we still have no efficient, approved treatment for autism spectrum disorders (ASD). The latest World Health Organization fact sheet states that ASD affects one in every 160 children worldwide (https://www.who.int/news-room/fact-sheets/detail/autism-spectrum-disorders), which affect 54–66 the USA. development molecular and genetic tools has helped to identify altered targets ASD, namely proteins involved synaptic transmission, but they not by providing candidates. our opinion, massive, excessive, reliance on promises novel mutations been translated into treatments, as all expected. It is possible there are more than 800 means short targets, an excess transgenic mice investigate. But identifying a mutation few with using animal models test can only be successful if underlying solid concept experimental evidence aim. failure develop treatments Rett or Fragile X syndromes, despite were identified decades ago, vivid illustrations difficulty directly translating these observations treatments. We suggested main problem develops utero, where it impact brain leads poorly formed misconnected neurons networks remain immature. These immature disturb generation oscillations essential behaviour, this implies drugs selectively block their activity promising approach. This neuroarchaeology concept1 validated experimentally. illustrates importance taking account dynamic sequence events generated insult. A recent review pointed out 90% clinical trials based preclinical translational research data failed discussed why happened.2 history bumetanide treat illustration how naïve ideas risky, nonestablished, concepts lead trials. First, showed depolarising excitatory actions due inhibitory transmitter Gamma Amino-Butyric Acid (GABA), because intracellular chloride levels.3, 4 Then, new benzodiazepines had paradoxical effects when GABA effects.5 If misplaced properties, then drug restores low levels should attenuate ASD. lot ifs, worth trying! (Figure 1). decided bumetanide, highly selective antagonist sodium–potassium–chloride co-transporter (NKCC1), patients After pilot open trial, carried single site multiple double-blind trial6 both provided positive results. Since then, many independent double blind randomised confirmed results7. Bruining et al. published result open-label study reported efficiently attenuated features tuberous sclerosis, without having occurrence seizures.8 Other imaging eye tracking trials, Hadjikhani al., perhaps, importantly, interesting directions mechanisms treatment.9 paper Fernell al.10 issue Acta Paediatrica interesting, extends previous observations. Admittedly, reports trial just six aged 3–14 years old, four important points highlight here. severe initial Childhood Autism Rating Scale (CARS) total score above 39. They also moderate intellectual disability some degree language disability. Second, none any other comorbidities, medical syndromes epilepsy, suggesting bumetanide's symptoms interferences. Third, authors used 0.5 mg twice-daily dose recommended most Fourth, was see parents wanted interrupt continue once finished after 3 months. addition classical Clinical Global Impressions (CGI) scale, Parental Satisfactory Survey, compromises large list items enables researchers determine whether consider improvement treatment. first time parental scale provides insights parents' perceptions benefits bumetanide. Bumetanide improved parenting CGI scores particular domains, interest world, attempts communicate, number words sounds clarity communication. improvements common reaction from treated present. Although findings small several limitations, adds information numerous autistic children. Large, well-conducted way address question proper manner. Therefore, European Medicines Agency paediatric investigation plan includes two phase III now being conducted Australia Europe, USA Brazil partnership comprises French pharmaceutical company Servier Neurochlore, biotech (http://autism-studies.com/). small, significant, testimony need conventional adolescents agents existing hypotheses, approach speculative, confident brains will developed coming years, incorporate notion intrauterine insult triggers cascade damaging deleterious sequelae. hypothesise inaugurating might underlie heterogeneity grateful Drs D Ferrari (Neurochlore), V Crutel S Kiaga (Servier) comments suggestions. Dr. C Dumon her help Figure.