Scientists replicate autism in monkeys

Chinese scientists have genetically engineered monkeys to show core symptoms of autism, according to a new study conducted at the Chinese Academy of Sciences and published in Nature. By using human gene therapy, the researchers, lead by Zilong Qiu of the Institute of Neuroscience at the Chinese Academy of Sciences, were able to create a line of cynomolgus monkeys, or crab-eating macaques, that expressed several core phenotypes of autism. The genetically-modified monkeys represent the first known primate model of autism, giving researchers a new tool through which they can better understand autism spectrum disorders.

The scientists used the human gene for Rett syndrome, a developmental disability similar to autism, to engineer monkeys that showed behaviors that are related to autism in human patients, including increased anxiety, repetitive behaviors and impaired social interaction.

The team began by injecting a non-lethal virus containing a copy of a human MECP2 gene, which is responsible for Rett syndrome, into maturing monkey eggs. Rett syndrome is a genetic disease affecting the gray matter of the brain. Human patients with Rett syndrome often exhibit autistic behaviors. After culturing the eggs and adding sperm to the culture, the researchers produced transgenic zygotes that overexpressed the human MECP2 gene. In the end, eight monkeys survived, with the MECP2 gene being most overexpressed in the cortex and cerebellum. When the monkeys reached 18 months of age, Qiu began testing them for cognitive and behavioral patterns that are commonly associated with autism to test the validity of his model.

Researchers studying autism have traditionally been faced with many challenges due to the heterogeneous nature of the disease, according to Dr. Martien Kas, associate professor of Translational Behavioral Genetics at the University Medical Center Utrecht, in an Oct. 2015 presentation at the Max Planck Institute of Psychiatry. Some children with autism predominantly show behaviors that are stereotypical of the disorder, while others may only exhibit certain deficits in their development of social behavior.

According to Kas, researchers that used human genetic studies have found more than 200 Autism Spectrum Disorder (ASD) risk genes. In spite of this genetic data, researchers have struggled to understand how these genetic mutations can lead to the behavioral and social problems observed in autism.

As a result of autism’s inherent complexity, pharmaceutical companies have long struggled to develop therapies for the disorder. Dr. Melissa Bauman, an assistant professor in the department of psychiatry and behavioral sciences at the University of California Davis, believes that the struggles with identifying treatments for autism may have something to do with the common use of mice to study autism.

“Given that Autism Spectrum Disorder is [a] uniquely human disorder characterized by deficits in complex behaviors, there are limitations in relying solely on mouse models,” Bauman told PBS. “Many pharmacological interventions developed in mice to treat human disease ultimately fail.”

Scientists hope that by using primate models, such as Qiu’s autistic monkeys, they may be able to better model autism and understand the molecular mechanisms leading to dysregulated social behavior.

“Mice are not in the same league when you’re talking about doing models of social cognition and interaction,” Dr. Jonathan Sebat, chief of the Beyster Center for Genomics of Psychiatric Disease at the University of California, San Diego (UCSD), told The New York Times. “It’s very logical that a primate would make a better model of human development and neurodegeneration. It’s a no-brainer.”

According to the National Institutes of Neurological Disease and Stroke, ASD refers to a group of complex neurodevelopment disorders that are characterized by repetitive patterns of behavior as well as issues with communication and social interaction. Qiu and his team used well-characterized tests for social behavior and anxiety to ensure that their transgenic monkeys showed signs of autism.

After observing their vocal patterns, the group found that the autistic monkeys made more grunts, coos and screams than non-autistic monkeys, which is indicative of increased social anxiety. The team also studied the monkeys’ social behavior by measuring the average time that a transgenic monkey spent interacting with a normal monkey over six months. Based of their results, the researchers found that the average time that a transgenic monkey sat with a normal monkey was significantly lower than the time that a normal monkey would sit with another normal monkey.

While Qiu’s study represents the first validated primate model of autism, some scientists remain skeptical when asked about this study’s implications for future research.

“It remains to be seen if the model can actually generate novel insights into the human condition,” Dr. Alysson Muortri, Associate Professor in the Department of Pediatrics and Cellular & Molecular Medicine at UCSD, told Nature.