Researchers at the University of California, Riverside, report in the journalNeurobiology of Diseasethey were able to ameliorate FXS symptoms after insertingFmr1into the brains of very young transgenic mice that had been genetically engineered to lack this gene. When the researchers measured brain activity for signs of anxiety and hyperactivity in response to stimuli such as stresses and sounds, they found that the reactivation of theFmr1gene in these mice had led them to no longer show FXS symptoms.

"Our work shows beneficial effects of reactivating theFmr1 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 laboratory, in collaboration with Khaleel A. Razak, a professor of psychology, selected very young mice -- less than 3 weeks old -- because brains are most plastic early in life; the equivalent in humans is around the first 3-5 years.

"For humans, the first 3-5 years are critical in brain development," Ethell said. "It's important, therefore, that this early period be targeted in FXS."

The mouse brain, like the human brain, has excitatory and inhibitory neurons. Unlike excitatory neurons that lead to a forward propagation of information, inhibitory neurons work like a brake by suppressing unnecessary activity and tuning brain activity to specific signals.

Ethell and two colleagues recently published a review article inNature Neuroscienceshowing that the dysfunction of inhibitory neurons is a common pathology in genetic diseases that are linked to autistic spectrum disorders, or ASD.

"In the current study, we targeted excitatory neurons in the second and third postnatal weeks of the mice to insert theFmr1 gene”,Ethell说。“我们的研究显示这一时期是否定的t 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."

How Ethell and her team introduced theFmr1 geneinto mouse brain differs from how the gene would potentially be introduced in a human brain. The final outcome, however, would be the same, Ethell said. According to her, CRISPR, a powerful tool for editing genomes, would most likely be used to reactivateFmr1in human brain.

"FXS is most often diagnosed early in a person's life," she said. "We cannot stress enough, therefore, that the early years are the perfect time to reactivate theFmr1 gene. It offers hope that even if this gene is missing in a child, it can still be introduced, allowing the child to live a daily life free of FXS. As gene reactivation to treat FXS receives increasing attention, our results suggest the benefits ofFmr1re-expression during the early period of brain plasticity in mice, which roughly corresponds to the first three years of human life, when ASD symptoms first emerge in infancy."

Next, the research team will work to restore function in the adult FXS brain.

"The main challenge is that the adult brain is not so plastic," Ethell said. "Young brains can do just about anything. But as an adult, have you tried to learn a new language?"

The research was funded by the National Institutes of Health, the Department of Defense, and the FRAXA Research Foundation. First author Maham Rais was also supported by a National Research Service Award Fellowship from the National Institute of Neurologic Disorders and Stroke.

Ethell, Razak, and Rais were joined in their study by Jonathan W. Lovelace, Xinghao S. Shuai, Walker Woodard, Steven Bishay, Leo Estrada, Ashwin R. Sharma, Austin Nguy, Anna Kulinich, Patricia S. Pirbhoy, Arnold R. Palacios, and David L. Nelson. Except for Nelson, who supplied the transgenic mice and is at the Baylor College of Medicine in Texas, all the coauthors are at UCR.

The research paper is titled "Functional consequences of postnatal interventions in a mouse model of Fragile X syndrome."