Investigators at Penn State identified a therapeutic approach that could have potential in treating Rett syndrome and other types of autism-spectrum disorders.
The team differentiated stem cells from the skin cells of patients suffering from Rett syndrome, creating nerve cells that were studied in the lab. Those nerve cells contained a mutation in the MECP2 gene believed to be linked to Rett syndrome. They found that the nerve cells lacked the KCC2 molecule. The results were published in the Proceedings of the National Academy of Sciences.
"KCC2 controls the function of the neurotransmitter GABA at a critical time during early brain development," said Gong Chen, a professor of biology and the Verne M. Willaman Chair in Life Sciences at Penn State. "Interestingly, when we put KCC2 back into Rett neurons, the GABA function returns to normal. We therefore think that increasing KCC2 function in individuals with Rett syndrome may lead to a potential new treatment."
Working with the knowledge that insulin-like growth factor 1 (IGF1) improved symptoms of Rett syndrome, the researchers found that when they used IGF1 to treat the nerve cells, they were able to boost levels of KCC2 and restore the GABA function.
Now the search is on for molecules that can target KCC2.
"The finding that IGF1 can rescue the impaired KCC2 level in Rett neurons is important not only because it provides an explanation for the action of IGF1," said Xin Tang, a graduate student in Chen's lab and the first-listed author of the paper, "but also because it opens the possibility of finding more small molecules that can act on KCC2 to treat Rett syndrome and other autism spectrum disorders."