Newly discovered drug target may lead to treatment for severe autism

Novel drug target may restore functional deficits in Rett Syndrome patients.

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Researchers from Penn State University (PA, USA) have utilized a novel drug target to rescue functional deficits in human nerve cells derived from patients with a severe form of autism-spectrum disorder, called Rett Syndrome. Their work could lead to a new treatment for Rett Syndrome and other autism-spectrum disorders.

Gong Chen, who led the team, explained, “The most exciting part of this research is that it directly uses human neurons that originated from Rett Syndrome patients as a clinically-relevant disease model to investigate the underlying mechanism. Therefore, the new drug target discovered in this study might have direct clinical implication in the treatment of Rett Syndrome and potentially for other autism-spectrum disorders as well."

The researchers took skin cells of patients with Rett Syndrome, and used them to differentiate stem cells into nerve cells to be studied in the laboratory. The nerve cells carry a mutation in the gene MECP2, believed to be the cause of most cases of Rett Syndrome. The researchers determined that these cells also lacked a molecule called KCC2 that is critical to normal nerve cell function and brain development.

"KCC2 controls the function of the neurotransmitter GABA at a critical time during early brain development. Interestingly, when we put KCC2 back into Rett neurons, the GABA function returns to normal,” Chen described. “We therefore think that increasing KCC2 function in individuals with Rett Syndrome may lead to a potential new treatment."

Chen’s team was also able to show that treating the diseased nerve cells with insulin-like growth factor 1 (IGF1) elevated the levels of KCC2 and corrected the function of GABA. IGF1 has been previously shown to alleviate symptoms of Rett Syndrome in mice, and is currently in Phase II trials for the treatment of the disease in humans.

Xin Tang, first author on the paper, concluded, "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, 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."

Stella Bennett


Discovery of a new drug target could lead to novel treatment for severe autism.

Tang, X., Kim, J., Zhou, L., et al. (2016). KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome. Proceedings of the National Academy of Sciences . doi:10.1073/pnas.1524013113. doi:10.1073/pnas.1524013113

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Stella Bennett

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