Researchers have identified a drug target with the potential to improve social interaction in people with certain forms of autism spectrum disorder (ASD).
For a study published in the journal Biological Psychiatry, the researchers used a mouse model to show how targeting the gene Protocadherin 10 (PCDH10) can lead to better levels of social interaction in individuals diagnosed with ASD.
According to Dr. Edward S. Brodkin, senior author of the study, their work could lead to a significant change in how the research community understands the causes of autism and the resulting brain changes.
"This research ... could lead to new treatment approaches for the harder-to-treat social aspects of ASD," he said.
A number of medications are already in place today to address symptoms like anxiety, irritability, depression and attention deficit hyperactivity disorder but there are currently none that have been specifically approved for treating core social interaction deficits in people with ASD. Additionally, it is not completely clear as to how social interaction symptoms manifest in the brain.
Earlier studies have previously implicated PCDH10 as having a role in the behavioral symptoms of individuals with ASD so the researchers decided to focus on it. A molecule responsible for neural cell adhesion, the gene is involved in synapse maintenance and brain development. It is also expressed in abundance in certain brain regions, like the amygdala, where motivation and emotion are mediated.
When one of the two PCDH10 copies was deleted in the model, the mice started showing a drop in social approach behavior resembling withdrawal in people with ASD. More of the male mice were affected too, which is consistent with the prominence of ASD in human males. Anomalies in the function and structure of the circuits of the amygdala were observed as well, plus lower levels of specific glutamate receptor subunits (known as NMDA receptor subunits) in that part of the brain.
But when the researchers administered a drug called d-cycloserine, they saw that the male mice improved in their social interactions. D-cycloserine works by binding to the NMDA receptor's glycine binding site. This results in higher levels of glutamate signaling at the receptors.
The results of Brodkin and colleagues' work match findings from preliminary studies in humans and d-cycloserine. According to these findings, significant improvement in social interactions in young adults and older adolescents with ASD was achieved with the drug. The researchers believe that the results of the current study can be used as proof to help propel further studies on humans and d-cycloserine.
In the future, the researchers also want to explore the underlying biological mechanisms that led to male mice showing worse social withdrawal symptoms than their female counterparts in the study, as this may help shed light on possible treatment options for addressing social withdrawal in specific subtypes of ASD.
