Promising results from early trial with bumetanide for autism in young children

A pilot study investigating the effects of bumetanide for autism in young children has produced promising results.

Autism, or “autism spectrum disorder” (ASD), is a brain development disorder that leads to behavior and communication problems. Children with ASD may have a range of symptoms including delay in speaking and difficulties in social interactions such as smiling, making eye-contact, or understanding emotions. They may be hypersensitive to stimuli such as noise or touch. Children with ASD may also have limited interests, become very upset with changes to their routine, or show repetitive behaviors such as rocking or repeating words. In mild ASD, people are often able to function independently as adults, but in severe cases, they need lifelong care and support. Early diagnosis and treatment of children with ASD improves their long-term prognosis.

Autism spectrum disorders may be linked to brain chemical imbalance

The underlying causes of ASD are unknown. Current treatment for children with ASD mainly involves behavioral therapies to improve and manage ASD symptoms. However, these therapies are often unavailable to children in poor or remote communities.

Some research suggests that an imbalance in certain chemical messengers in the brain, in particular, GABA and glutamate, may affect nerve cell development and function. Drugs that restore the correct GABA/glutamate neurochemical balance may offer a new way to treat for ASD.

Laboratory studies with the drug bumetanide, normally used to treat body fluid retention, showed that it improved symptoms in animal models of ASD. Initial small clinical trials showed that bumetanide improved symptoms in children with ASD. However, these trials did not measure the effects of bumetanide on the GABA/glutamate balance in the brain. Researchers at the Universities of Cambridge (UK) and Shanghai Jiao Tong (China) collaborated in a pilot study looking at the effects of bumetanide for autism in young children. They recently published their findings in Translational Psychiatry.

Bumetanide improved ASD symptoms and decreased brain GABA/glutamate ratios

The researchers studied 83 children with ASD, aged three to six years old. At the start of the study, all children were assessed using the Childhood Autism Rating Scale (CARS), a standardized test that rates ASD symptom severity. The children also had brain scans to measure the GABA to glutamate ratio levels in two areas of the brain: the insular cortex – involved in emotional responses and the visual cortex –which processes visual information.

A treatment group of 42 children received 0.5 mg of bumetanide twice a day for three months, whilst the control group (41 children) received no drug treatment. After three months, the children in the bumetanide group had improved CARS scores compared to the control group. Brain scans of the insular and visual cortices showed that the GABA/glutamate ratios in these areas had decreased more rapidly over three months in the bumetanide group compared to the control group. No significant side effects were reported in children taking bumetanide.

Further research on bumetanide for autism is needed to confirm these promising results

“This is the first demonstration that bumetanide improves brain function and reduces [ASD] 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,” said Prof. Ching-Po Lin, one of the lead authors of the study.

Prof. Barbara Sahakian, from the University of Cambridge added, “This study is important and exciting because it means that there is a drug that can improve social learning and reduce ASD symptoms during the time when the brains of these children are still developing.” It is known that GABA and glutamate are key neurochemicals for brain plasticity and learning. Early treatment to rebalance these chemicals may help children with ASD to have a better quality of life. The finding that bumetanide changes the GABA /glutamate ratio concentrations may also provide a way to measure the treatment’s effectiveness.  However, the researchers caution that further studies in a larger number of children are needed to confirm whether bumetanide is an effective and safe treatment for children with ASD.

Written by Julie McShane, MA MB BS

References:

1. Zhang LL, Huang CC, Dai Y, et al. Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios. Translational Psychiatry 10, Article number: 9 (2020). Doi: https://doi.org/10.1038/s41398-020-0692-2.
2. University of Cambridge. Press release, 26 Jan 2020. “Prescription drug improves symptoms of autism by targeting brain’s chemical messengers.” https://www.eurekalert.org/pub_releases/2020-01/uoc-pdi012320.php

Image by Rudy and Peter Skitterians from Pixabay