Prescription drug bumetanide could help treat autism

By Dr. Liji Thomas, MDJan 26 2020

A new drug called bumetanide, which is used to treat edema, shows promise in treating some symptoms of autism in young children, while not showing significant adverse effects. The study was published in January 2020 in the journal Translational Psychiatry.

What is ASD?

Autism spectrum disorder (ASD) is a disease that causes neurologic and developmental delay, in about 1 of 160 children all over the world. Its primary characteristics are poor social communication, restricted interests, and stereotyped behavior. The social impairment shows as difficulty in nonverbal communication and with emotional sharing, such as occurs with eye contact and with smiling. It results in the inability to develop and keep up social relationships, and to understand them in others.

Image Credit: Zahraa Saleh / Shutterstock

ASD covers a wide spectrum of severity. With mild ASD, independent or adaptive behavior is possible. With more severe ASD, independent living may be impossible, and the individual may require to be cared for throughout life.

The biology underlying ASD is far from clear. However, some scientists think on the basis of earlier work that it is the result of abnormal brain development in very early life, relating to a neurotransmitter called GABA, which regulates the communication of nerve cells. GABA is an excitatory chemical in the fetus and soon after birth. It stimulates nerve cells and impulse production, helping the nerve pathways to develop and mature. On the other hand, in adult life it plays an inhibitory role. If this switch doesn’t occur normally, it could delay the point at which the neural networks in the brain become functionally mature, thus depressing the level of activity within the network.

Thus, it could be very helpful to introduce drugs earlier, to facilitate this switch at a normal age, and thus prevent the development of some of the symptoms that are hardest to deal with in people with ASD. At present, most preschool ASD therapies center around behavioral therapies, such as parent-child play and shared activities. This is supposed to increase the level of skill in language, cognition and social areas. The extent to which such therapies can be accessed by ASD patients varies widely with the environment, however, and children in low- and middle-income countries probably aren’t offered such treatments for the most part.

The study

Older rat studies and a few clinical trials on ASD children have focused on bumetanide. This served as the motivation for the current study, which centered on safety and efficacy assessments. The study looked at 83 children aged 3-6 years. They were randomly assigned to either of two groups. The treatment group (group 1) got bumetanide at 0.5 mg twice a day, for 3 months. The control group (group 2) was left untreated.

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.