The researchers used the Childhood Autism Rating Scale (CARS) to assess their behavior in terms of imitative behavior, emotional response and communication, both verbal and non-verbal. Any score above 30 is an indication of ASD. The findings
The CARS scores in both groups were similar. However, following the 3 months course of bumetanide, the mean score was 34.5 for group 1 compared to 37.3 in group 2. A more significant change was the decrease in the number of CARS items that scored 3 or more, to 3.5 on average in group 1 compared to 5.5 items on average in group 2. The mechanism
Having seen the improvement, the scientists now set out to understand what brought about the change. They used magnetic resonance spectroscopy, a brain imaging technique, that could show the levels of various neurotransmitters in the brain. The results showed that bumetanide treatment caused a reduced ratio of GABA to glutamate over the period of treatment, in two brain areas. One is the insular cortex, which is involved in our feelings, empathy and being aware of oneself. The other is the visual cortex which integrates and processes what we see.
The GABA-glutamate ratio is important because these chemicals are required for normal brain plasticity – the development of new brain pathways in response to new information and stimuli – and to enhance learning. Thus, this treatment should help these children to learn better, enjoy a higher quality of life, and feel a greater sense of wellbeing. The implications
Researcher Ching Po-Lin is excited about the finding because it shows, for the first time ever, that any drug can improve ASD symptoms and promote social integration during the period of development of the child’s brain. He says: “This is the first demonstration that bumetanide improves brain function and reduces symptoms by reducing the amount of the brain chemical GABA. Understanding this mechanism is a major step towards developing new and more effective drug treatments."
The change in the GABA-glutamate ratio could serve as a biomarker to measure the efficacy of treatment as well. The researchers will continue to work on the effectiveness of this drug, to confirm their results.
Researcher Fei Li comments: “I have many children with autism spectrum disorder under my care, but as psychological treatment resources are not available in many places, we are unable to offer them treatment. An effective and safe treatment will be very good news for them.” She cites the case of a 4-year-old boy who improved significantly with the use of bumetanide, becoming better at making eye contact with family and relatives as well as sharing in activities with them. She says she wants to make sure all families with autistic children can get this treatment, wherever they live. Journal reference:
Lingli Zhang et al. Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios. Translational Psychiatry; 27 Jan 2020, https://www.nature.com/articles/s41398-020-0692-2
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