autism
The Shank3 gene is critical for brain developmentistock

Behaviours associated with autism, like repetitive actions and avoiding social interaction, have been reversed by flipping on a genetic switch in mice. When researchers at MIT turned on the Shank3 gene – which is involved in some types of autism in humans – these behaviours were eliminated, a finding that could lead to future treatments of the disorder.

The Shank3 gene is critical for brain development. About 1% of people with autism are missing this gene – about 7,000 people in the UK and 35,000 in the US. The gene is found in the connections that allow neurons to communicate with each other, organising proteins needed to coordinate a neuron's response to signals. Without this gene, people normally develop autism-like symptoms such as repetitive behaviours, increased anxiety and the avoidance of social interaction.

In a study published in the journal Nature, scientists turned off the Shank3 gene in mice at the embryonic stage, but in a way that it could be turned back on at any time using tamoxifen. As juveniles, these mice displayed autism-like behaviours. When the mice were between two and four months, the team switched on the gene. After doing so, the mice stopped carrying out repetitive behaviours and became more social.

Previously, scientists had shown mice without the Shank3 gene had a greatly reduced density of dendritic spines in part of the brain called the striatum. These spines are small buds on the surface of neurons that help synaptic signal transmission.

When the Shank3 gene was turned on, the density of dendritic spines increased dramatically. This, the team say, shows the plasticity in the adult brain. However, other behaviours, including anxiety and poor motor coordination did not disappear. When the team turned the gene back on earlier in life (20 days) this improved to some extent, but did not go away altogether.

Lab Mouse
Scientists turned off the Shank3 gene in mice at the embryonic stage, but in a way that it could be turned back on at any time using tamoxifeRama/Creative Commons

This indicates these behaviours rely on circuits that are formed during early development. "Together, these results reveal the profound effect of post-developmental activation of Shank3 expression on neural function, and demonstrate a certain degree of continued plasticity in the adult diseased brain," the team wrote.

They are now looking to find the critical periods of the formation of these circuits in order to find the right time to intervene. "Some circuits are more plastic than others," study author Guoping Feng said. "Once we understand which circuits control each behavior and understand what exactly changed at the structural level, we can study what leads to these permanent defects, and how we can prevent them from happening.

"There is more and more evidence showing that some of the defects are indeed reversible, giving hope that we can develop treatment for autistic patients in the future." For the people with Shank3 mutations, the find indicates some genome-editing techniques could be employed to repair it and improve some symptoms, even in adults.

Feng also says the study could have wider implications for autism. If they are able to identify circuits specific to behavioural abnormalities and how to modulate these circuits, they could help other people who have defects in these areas – even though the defects do not result from the genetic mutation.

Gordon Fishell, a professor of neuroscience at New York University School of Medicine, commented: "Feng's demonstration that restoration of Shank3 function reverses autism symptoms in adult mice suggests that gene therapy may ultimately prove an effective therapy for this disease."