Expert Alysson R Muotri The neurological disorder, Rett (RTT) syndrome probably reveals behavioral symptoms after six months to 1½ years of age. Along with progressive decline in motor functions, the disease may also lead to hypotonia or low muscle tone, seizures, diminished social skills and other autistic behaviors. Experts from the University of California, San Diego School of Medicine have apparently designed functional neurons for understanding the development of autism spectrum disorder (ASD).

Crafted with the help of induced pluripotent stem cells from patients diagnosed with RTT syndrome, the tool may be employed for drug screening, diagnosis and personalized treatment. During the research, investigators employed induced pluripotent stem cells (iPSCs) for developing a culture system. The stem cells giving rise to connective tissues were achieved from RTT patient’s skin fibroblasts. On reprogramming the human RTT-iPSCs, researchers compared them to normal control cells. Lesser synapses, decreased spine density, smaller soma size, altered calcium signaling and electrophysiological defects appeared. All these factors supposedly indicate that the deleterious changes to human RTT neurons begin early in development.

Alysson R. Muotri, PhD, assistant professor of pediatrics, and lead investigator, elucidated, “This work is important because it puts us in a translational mode. It helps expand and deepen our understanding of autism, from behavioral disorder to developmental brain disorder. We can now look for and test drugs and therapies and see what happens at a cellular and molecular level. That’s something we’ve never been able to do with human autistic neurons before.”

In the course of the research, experts also shed light on human RTT-iPSCs to insulin growth factor 1 or IGF1. A mouse model with RTT syndrome was included in the investigation for examining whether IGF1 enhances symptoms. Reportedly the protein has similar potential for treating RTT and other neurological disorders. It was suggested that synaptic deficiencies noted in Rett syndrome are temporary. IGF1 seemingly rescues some RTT-iPSCs and corrects certain neuronal defects, but the way it works is not known.

The research is published in the November 12 issue of the journal Cell.