Penn State University scientists have discovered a novel drug target and have rescued functional deficits in human nerve cells derived from patients with Rett Syndrome, a severe form of autism-spectrum disorder.
The researchers differentiated stem cells derived from the skin cells of patients with Rett Syndrome into nerve cells that could be studied in the laboratory. These nerve cells carry a mutation in the gene MECP2, and such gene mutations are believed to be the cause of most cases of Rett Syndrome. The researchers discovered that these nerve cells lacked an important molecule, 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," author said. "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."
The researchers also showed that treating diseased nerve cells with insulin-like growth factor 1 (IGF1) elevated the level of KCC2 and corrected the function of the GABA neurotransmitter. IGF1 is a molecule that has been shown to alleviate symptoms in a mouse model of Rett Syndrome and is the subject of an ongoing phase-2 clinical trial for the treatment of the disease in humans.