A controversial new study is being carried out, at the Shanghai Institutes for Biological Sciences, on monkeys that have been genetically modified to have the behavioural traits of human autism. Autism is a developmental disorder that influences how a person relates to and communicates with others.
The researchers added a gene that is known to cause autistic symptoms in humans, creating what they believe to be the best animal model to date. The monkeys’ symptoms, including running in circles, disregarding the other monkeys and grunting, showed different degrees of severity.
Their research goal now is to use these monkeys to find ways to treat the illness in humans. Unlike previous studies, they created a large enough group to be able to study trends in their behavior. Looking at the genetic changes in the severe cases, and reversing those changes, is the team’s plan for research.
Upwards of 100 genes are thought to contribute to autism. The gene that these researchers altered was MECP2. In humans, it can be mutated or duplicated, both of which cause conditions with symptoms similar to those of autism. The monkeys in this study have extra copies of the gene.
The work all began six years ago, when the scientists injected monkey eggs with an innocuous virus attached to human MECP2 genes. These eggs were then implanted in the monkey mothers, and eight genetically modified babies were spawned, each with at least one and up to seven additional copies of MECP2.
A year later, the researchers observed unusual behaviour in the new generation of monkeys. Conducted batteries of behavioral tests showed that all the monkeys had at least one symptom also found in autism, including difficulties with social interaction, and repetitive behaviors.
This first submission of the paper, however, was rejected. Reviewers wanted clear evidence that the behavior was due to the genetic change. When the next generation of monkeys was born, exhibiting similar symptoms, the researchers now had a convincing case. This was not the first study that engineered monkeys with genes related to autism, but never before had the genes been linked with behavior.
The next stage of research is to figure out which brain areas or networks are causing these autism-like symptoms, test treatments to correct these areas, and observe if behavioral changes disappear. They are currently performing brain imaging to pinpoint the differences in the monkeys’ brains.
Further down the line, the scientists plan on using the powerful new technique, CRISPR, to remove the extra copies of MECP2 in the relevant regions of the brain, and see if the behaviors change. Possible treatments could include electrical stimulation deep into the brain, magnetic stimulation across the skull, or gene therapy, which might involve CRISPR.
The use of monkeys in research is controversial, so autism research has also been conducted on mice. However, their brains are very different from ours. This divergence is especially problematic for psychiatric disorders, which affect higher level functions that do not exist in mice.
People with autism vary in their symptoms and the illness can be linked to other conditions. This is another reason why creating a single animal model might be difficult. However, using monkeys as a model organism might prove promising both in autism and other mental and psychiatric disorders that cannot be studied in other organisms.
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