Study discovers new drug target may lead to development of new treatment for severe autism

Patients with severe autism could soon access a new and potentially effective treatment to relieve effects of the condition with the discovery of a new drug target by scientists at Pennsylvania State University in the US. The new target could potentially lead the development of a new drug for a severe form of autism-spectrum disorder called Rett Syndrome and other forms of the disorder.

A new study, published in the journal Proceedings of the National Academy of Sciences, shows the success of the researchers to directly use neurons from Rett Syndrome patients to analyse the condition.

The researchers examined stem cells from the skin cells of the patients and their nerve cells which carry a mutation in the gene MECP2. This gene mutation is considered to be the potential cause of Rett Syndrome.

The nerve cells were also found to lack the important molecule known as KCC2, which is significant for normal nerve cell function and brain development. During early brain development, KCC2 plays a key role in regulating the function of the neurotransmitter GABA, researchers said.

"Interestingly, when we put KCC2 back into Rett neurons, the GABA function returns to normal,” said lead researcher Gong Chen, a professor of biology at Penn State University. The team believes that improving the function of KCC2 in Rett Syndrome patients may lead to a potential new treatment.

"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," Chen said.

Furthermore, the study also shows the KCC2 level has increased when diseased nerve cells were treated with insulin-like growth factor 1 (IGF-1), a molecule that can alleviate symptoms of Rett Syndrome in a mouse model. The use of IGF-1 has also corrected the function of the GABA neurotransmitter.

IGF-1 is currently on the phase 2 clinical trial of a treatment for the disease in humans.

"The finding that IGF-1 can rescue the impaired KCC2 level in Rett neurons is important not only because it provides an explanation for the action of IGF-1 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," said Xin Tang, a graduate student in Chen's Lab.