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Researchers study Rett neurons in a Petri dish

November 19, 2017

Marchetto started with skin biopsies taken from four patients carrying four different mutations in the MeCP2 gene and a healthy control. By exposing the skin cells to four reprogramming factors, she turned back the clock, triggering the cells to look and act like embryonic stem cells. Known at this point as induced pluripotent stem cells, the Rett-derived cells were indistinguishable from their normal counterparts.

It was only after she had patiently coaxed the iPS cells to develop into fully functioning neurons-a process that can take up to several months-that she was able to discern differences between the two. Neurons carrying the MeCP2 mutations had smaller cell bodies, a reduced number of synapses and dendritic spines, specialized structures that enable cell-cell communication, as well as electrophysical defects, indicating that things start to go wrong early in development.

Since insulin-like growth factor 1 (IGF-1)-a hormone which, among other things, has a role in regulating cell growth and neuronal development-was able to reverse some of the symptoms of Rett syndrome in a mouse model of disease, the Salk researchers tested whether IGF-1 could restore proper function to human Rett neurons grown in culture.

"IGF-1 treatment increased the number of synapses and spines reverting the neuronal phenotype closer to normal," says Gage. "This suggests that the autistic phenotype is not permanent and could be, at least partially, reversible."

Muotri is particularly excited about the prospect of finding a drug treatment for Rett syndrome and other forms of autism: "We now know that we can use disease-specific iPS cells to recreate mental disorders and start looking for new drugs based on measurable molecular defects."

Source: Salk Institute