Hope for drug treatments for autism following new genetic discovery


Scientists at Lancaster University have discovered, for the first time, how a genetic change associated with cognitive deficits and the risk of certain neurodevelopmental disorders affects brain function, opening up the possibility of new drug treatments for neurodevelopmental disorders such as autism.

for their research, Posted in autism research, scientists explored the expression of the Neurexin 1 gene and demonstrated how reduced expression of this gene in mice impacts the prefrontal cortex and impairs cognitive flexibility.

Specifically, they demonstrated that deleting the Neurexin1 gene reduces glucose metabolism in the prefrontal cortex, the area involved in higher-level cognitive functions, including attention and cognitive flexibility. They also found that the reduction in glucose metabolism in the prefrontal cortex resulting from the deletion was linked to the fact that the male mice became hyperactive when faced with new situations.

The authors said people with a DNA deletion at chromosome 2p16.3, which results in the deletion of the Neurexin1 gene, often experience neurodevelopmental delay and cognitive problems. Those with the 2p16.3 deletion are about 14 to 20 times more likely to develop neurodevelopmental disorders, such as autism, than people without the deletion.

Effective drug treatment needed

Certain genetic changes are known to both cause neurodevelopmental problems and greatly increase a person’s risk of developing disorders such as autism, schizophrenia and Tourette’s syndrome. However, although an estimated 2-3 million people worldwide suffer from this type of DNA deletion, “there are currently no effective drug treatments for the resulting cognitive problems,” the authors said. .

In addition to demonstrating that deleting the Neurexin1 gene reduces glucose metabolism in the prefrontal cortex, they also found that it reduces insulin signaling receptors in the prefrontal cortex. This, they said, “probably underlies the reduced glucose metabolism seen in this region.”

Their findings open the door to potential new drugs that increase insulin signaling for use in treating autism and other neurodevelopmental disorders.

Lead researcher Dr Neil Dawson of Lancaster University said: “There is an urgent need to better understand the underlying neurobiology of neurodevelopmental disorders in order to develop new treatments.”

The key finding that deletion of Neurexin1 impacts insulin signaling and glucose metabolism in the prefrontal cortex suggests that using drugs to increase insulin signaling may be an effective therapeutic strategy.

Dr. Dawson pointed out that medications to help people with cognitive and social issues are especially needed because these symptoms have a huge impact on a person’s quality of life.

Dysfunctional serotonin neurotransmitter system

The scientists identified a second brain region impacted by the deletion of Neurexin1 – the dorsal raphe, which showed increased activity. This region, they explained, is the source of serotonin neurons that project throughout the brain. This suggests that deletion of Neurexin1 also renders the serotonin neurotransmitter system dysfunctional.

Dr Dawson said: “The observation that the serotonergic system may be dysfunctional requires further research and suggests that drugs targeting this neurotransmitter system may also be useful.”

The authors concluded that targeting the prefrontal cortex and the serotonergic system may be a useful therapeutic strategy for people with 2p16.3 deletion and associated neurodevelopmental disorders.

Dr Dawson said: “We can now test the ability of drugs that target these mechanisms to restore these translational changes seen as part of ongoing research to develop better treatments for people with 2p16.3 deletion, autism, schizophrenia and Tourette syndrome.


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