In an impressive new trial with mice, researchers have successfully reversed the symptoms of autism simply by switching on a specific gene. Although human trials are a long ways away, the researchers are excited by the results since the autism symptoms disappeared in both young and old mice — hinting that adult brains are more malleable than previously thought, and the frustrating symptoms of autism could potentially be eliminated even in older people.
"This suggests that even in the adult brain we have profound plasticity to some degree," said lead researcher Guoping Feng, professor of brain and cognitive science at MIT, in a press statement. "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."
The researchers engineered mice to be born without a gene called Shank3, which has been linked to autism in several studies and is estimated to be missing in 1 percent of autism patients. By turning the gene back on like a light switch, the scientists showed that various symptoms associated with autism could be stopped, like compulsive and repetitive behavior and the avoidance of social interaction.
Shank3’s job is to code for a protein that works in the synapses between brain cells, so it’s important for proper communication between the cells. The researchers found that brain cells didn’t grow properly in the mice who were engineered without Shank3, particularly in a brain region involved with the reward system, called the striatum.
These engineered mice also demonstrated a number of the characteristic behaviors seen in those with autism spectrum disorders, like anxiety, compulsive repetition of tasks, and social avoidance.
However, some of these symptoms disappeared after the team switched the gene back on in mice aged between two and 4.5 months (which is an adult in mouse years) simply by giving the mice tamoxifen, a drug used to treat breast cancer. The mice showed less compulsive grooming and interacted more with each other.
In fact, the scientists suggest that turning on the gene actually caused the brain to rewire itself, due to the fact that they saw an increase in the number of dendritic spines — the little branches that neurons use to communicate with each other.
Unfortunately, not all of the symptoms associated with autism disappeared. The researchers observed that the mice still showed signs of anxiety and some motor coordination problems. Feng hypothesizes that these behaviors likely rely on certain circuits that were irreversibly formed during early development.
“Some circuits are more plastic than others,” Feng says. “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.”
The team found that these symptoms could only be eliminated by switching on Shank3 earlier in development, just 20 days after birth. The team hopes to conduct further research to better understand this critical period during which certain autism symptoms are still malleable, and hopefully discover how to reverse symptoms in all individuals who struggle with autism instead of only those who are missing Shank3.
"The combination of behaviour, circuits, physiology, and genetics is state-of-the art," said neuroscientist Gordon Fishell from New York University School of Medicine, who wasn't involved in the study. "Moreover, 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."
Feng is confident that, some day, scientists may also eventually develop more general approaches to treating autism.
“That’s why it’s important in the future to identify what subtype of neurons are defective and what genes are expressed in these neurons, so we can use them as a target without affecting the whole brain,” Feng says.
Although it will be awhile before the research is ready for human trials, it’s an exciting leap forward in understanding a complicated neurodegenerative disorder that has become about 10 times more common over the past 40 years. Hopefully, over the next few years, we see scientists inch closer and closer to solving the mystery of autism.