A new FRAXA-funded research project offers hope that Fragile X syndrome could be treated by reactivating the gene which is shut down in people with the syndrome.
Researchers at the University of California, Riverside report in the journal Neurobiology of Disease and UC Riverside News that they were able to reduce FXS symptoms by inserting the FMR1 gene into the brains of very young mice. These mice had been genetically engineered by Dr. David Nelson to lack this gene, also with FRAXA funding.
“Our work shows beneficial effects of reactivating the FMR1 gene, which would be very welcome news for young children living with FXS,” said Iryna M. Ethell, a professor of biomedical sciences in the UCR School of Medicine, who led the research.
In their study, Ethell’s team, in collaboration with Khaleel A. Razak, a professor of psychology, selected very young mice — less than 3 weeks old — because brains are most adaptable early in life. The human equivalent is ages 3-5.
When the researchers measured brain activity for signs of anxiety and hyperactivity in response to sounds and other stresses, they found that the mice with a reactivated FMR1 gene no longer showed Fragile X symptoms.
CRISPR as a Genome Editing Tool
The method Ethell and her team used to introduce the FMR1 gene into the mouse brain would not be possible in humans. The final outcome, however, would be the same, Ethell said. She added that CRISPR, a powerful tool for editing genomes, would most likely be used to reactivate FMR1 in the human brain.
What’s Next for this Research?
The research team will next attempt to restore function in the adult FXS brain in mice.
“In the current study, we targeted excitatory neurons in the second and third postnatal weeks of the mice to insert the Fmr1 gene,” Ethell said. “Our study shows this period is not too late for manipulating the brain. We targeted these particular neurons because they establish a control over inhibitory neurons that are malfunctioning in FXS. At this time, we do not know if our method would be effective in adults. That research would be a next step in this line of work.”