Insulin-regulating drugs could help treat autism

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Drug-deletion of the Neurexin1 gene, which reduces glucose metabolism in the brain’s prefrontal cortex, could be an effective therapeutic strategy for neurodevelopmental disorders such as autism.

Autism spectrum disorders, schizophrenia or Tourette syndrome, among others, are related to genetic changes that cause problems in neurological development. For this reason, understanding the genetics of disorders such as autism is key to creating new therapies, or even to using some drugs that are already used in the treatment of other diseases. In fact, a new study from Lancaster University has found that drugs that increase insulin signaling may be effective in treating autism.

Researchers have discovered how a genetic change impacts insulin signaling and glucose metabolism in the brain. It was already known that small sections of DNA are duplicated or deleted in some people and this phenomenon, known as copy number variation, significantly increases the risk of developing these disorders.

For example, people with a DNA deletion on chromosome 2p16.3, resulting in the deletion of the Neurexin1 gene, typically have neurodevelopmental delays and cognitive problems, and people with the 2p16.3 deletion also have 14 to 20 times more likely to develop neurodevelopmental disorders, such as autism, schizophrenia, and Tourette syndrome, than people without the deletion.

Deleting a gene that increases the risk of neurodevelopmental disorders

The new research has shown for the first time that deleting the Neurexin1 gene reduces glucose metabolism in the prefrontal cortex, a key area of ​​the brain involved in high-level cognitive functions, including cognitive flexibility and attention. Deletion of this gene has also been found to decrease insulin receptor signaling in the prefrontal cortex, which likely underlies the reduced glucose metabolism seen in this brain area.

“There is an urgent need to better understand the underlying neurobiology of neurodevelopmental disorders in order to develop new treatments”

The study results, which have been published in Autism Research, provide valuable new insight into how this leads to cognitive deficits and behavioral changes and significantly increases the risk of developing various neurodevelopmental disorders. The fact that Neurexin1 deletion affects insulin signaling and glucose metabolism in the prefrontal cortex suggests that using drugs to increase insulin signaling could be an effective therapeutic strategy.

Dr Neil Dawson, from Lancaster University and lead author of the study said: “There is an urgent need to better understand the underlying neurobiology of neurodevelopmental disorders in order to develop new treatments. Medicines are especially urgently needed to help people with their cognitive and social problems, as these symptoms have a dramatic impact on their quality of life.”

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