A neurotransmitter receptor gene called mGluR5 was edited, which reduced the repetitive behaviour of mice with fragile X syndrome. This condition affects about 2 percent of people who have autism.
The scientists injected gold nanoparticles to deliver the CRISPR/Cas9 system to mice's brains. This meant that the researchers could precisely control how much of the Cas9 protein – which cuts the DNA – was delivered.
This approach halved levels of the mGluR5 protein in the mice and significantly reduced repetitive behaviours associated with autism spectrum disorder. It resulted in a 30 percent reduction in repetitive digging and a 70 percent decrease in leaping. Using the 'CRISPR-gold' method (see BioNews 921) also avoids problems with viral delivery systems, which can have higher toxicity and trigger an immune response.
'There are no treatments or cures for autism yet, and many of the clinical trials of small-molecule treatments targeting proteins that cause autism have failed,' said study leader Dr Hye Young Lee, an assistant professor of cellular and integrative physiology at the University of Texas Health Science Center at San Antonio. 'This is the first case where we were able to edit a causal gene for autism in the brain and show rescue of the behavioural symptoms.'
Fragile X syndrome is caused by a single-gene mutation. In most cases, autism spectrum disorder is a complex developmental condition, with both genetic and environmental influences. In many cases, there are multiple genes that play a role in the condition. In total, there are around 700,000 people with autism in the UK.
The lab is currently working on a way of delivering the nanoparticles via an injection into the spinal cord rather than through the skull into the brain. At the moment, however, much more work is needed before the trials progress to humans. The authors hope that the same approach could also be used to treat other diseases caused by a known single gene.