Scientists in China have engineered monkeys with a human autism gene and symptoms in the hopes of unlocking a treatment for the debilitating but little-understood disorder, a study said Monday.
The study was carried out by researchers from the Chinese Academy of Sciences and Fudan University and published in the peer-reviewed scientific journal Nature. The team, led by Zilong Qiu of the Institute of Neuroscience in Shanghai, created special test tube monkeys, giving them multiple copies of the MECP2 gene thought to be linked to autism in humans. The monkeys were born by surrogate females and their behavior studied as they grew up.
The authors stated, “Our findings pave the way for the efficient use of genetically engineered macaque monkeys for studying brain disorders.”
The “transgenic” macaques behaved similarly to humans afflicted with autism, the team wrote, including pacing in circles and interacting less with other monkeys. They became stressed more easily when researchers stared them in the eyes. The abnormal monkeys would “grunt, coo, and scream” more often if challenged in this way, according to Qiu’s team, and two became “severely sick” in ways that “echoed” the problems human children with the gene defect.
Qiu said during a conference call organized by Nature, “The monkeys show very similar behavior [to] human autism patients. We think it provides a very unique model.”
This meant they could serve as a reliable animal model for researching the causes of, and possible cures for, autism in humans.
Until now, animal studies of autism have relied mainly on lab mice, a species vastly different from humans in terms of genes, behavior, and physiology. Mice have very different brains from our own. For instance, they lack a prefrontal cortex, the brain area where some human psychiatric disorders seem to be centered. The Guardian reported that the research paves the way for more varieties of GM monkeys that develop different mental and psychiatric problems, which are almost impossible to study in other animals.
Qiu says that’s the reason his institute chose to create autistic monkeys. He says scientists would now be able to study what brain networks had been disrupted, as well as try out treatments such as deep-brain stimulation. Qiu says his group would also attempt to reverse the symptoms it created by erasing the genetic error in live animals. That could be done using new genome-editing technologies such as CRISPR.
Chinese Scientists Create 'Autistic' Monkeys In 'Cruel' Research Study Slammed By Cruelty Free International https://t.co/djgZBDBCDU
— Stephen Kuusisto (@StephenKuusisto) January 29, 2016
One of the monkeys transferred the transgene to its offspring, which also displayed autistic behavior, strengthening the hypothesis of a genetic root for autism, the study authors said.
Qiu said the team would now scan the brains of their monkeys to try and identify circuit deficiencies.
He explained, “Once we identify this brain circuit (problem) associated with the autism-like behaviour, we will use therapeutics such as gene editing tools… to manipulate this MECP2 transgene in the transgenic monkey.”
Qiu insisted the team’s methods met international ethical standards.
Other scientists hailed the study as an “exciting development.”
James Cusack, the research director at the autism charity Autistica, said through the Science Media Centre, “Developing sophisticated animal models of autism has always represented a significant challenge for scientists. This excellent research has developed a more sophisticated model of autism which may further our understanding of autism and could eventually lead to the development of more tailored treatments.”
University of California psychiatry professor Melissa Bauman said the work “opens the possibility to explore genetic risk factors in a species more closely related to humans.”
The MIT Technology Review reported that some scientists questioned whether the model developed in China was close enough to autism to really shed any light on human disease.
Huda Zoghbi, whose lab at the Baylor College of Medicine discovered in 1999 that damage to the MECP2 gene causes Rett syndrome, a form of autism affecting girls, said, “I think we need to be cautious calling this a model … it does not quite accomplish that.”
Humans can suffer a range of behavioural anomalies under the umbrella of autism spectrum disorder (ASD). Often sufferers are unable or unwilling to communicate or interact with others, have delays in cognitive development, or have dazzling gifts in fields such as maths or music. The brain structure of autism sufferers is different to that of other people, but the exact cause remains unclear, though genetics are strongly implicated. There is no cure, and behavior therapy is the main intervention. This study on autistic monkeys could provide a key to this condition.
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