First Human Cellular Model Created to Test Autism Drugs

“We always wanted to understand psychiatric disorders such as autism, but it’s hard because we have two options,” pediatrics assistant professor Alysson R. Muotri said. “One is to go for a mouse model, but [it’s] limited, especially in cases such as autism where there’s impaired social communication so animals don’t talk [and] they don’t have human language so it’s hard to do this study on animal models.”

Muotri said another way to analyze the effects of autism was by using brain tissue from someone who has died.

“However, when you have a postmortem brain, the damage is already there so you don’t understand how you get the disease because you have the endpoint,” Muotri said.

The stem cells came from connective skin tissue cells called fibroblasts in adult patients who had Rett syndrome. Rett syndrome is a severe neurodevelopment disorder similar to autism where motor functions and social skills are impaired.

The researchers worked with Salk Institute for Biological Studies and Pennsylvania State University to transform the cells into embryonic stem cells — specifically, induced pluripotent stem cells, which can artificially generate into different cell types — to turn them into neurons, which are signaling cells in the nervous system.

The neurons made up an autistic neuron model that researchers used to test drugs and therapies to study how they affect autism.

“The dream was to have a very naïve cell that you can drive the cells to become neurons and to express the autistic features,” Muotri said. “One way to do that is to use human embryonic stem cells.”

The researchers then saw symptoms of Rett syndrome in abnormal neurons — which were smaller than healthy ones, had fewer synapses and had communication failures. These are similar to the effects observed in mouse models.

Scientists then used the drugs used in mice to treat signs of autism and found that the abnormalities in the neurons were reversed.

“Because we can see the difference, then we can use a drug treatment to see if we can reverse the autistic phenotype back to normal,” Muotri said. “We did that using two different drugs [which] made the autistic cells grow into normal ones.

Muotri said one of the drugs he tested was in clinical trials for Rett syndrome and was only tested on mouse models. The other drug targeted a mutation associated with autism.

Since the researchers could see the reversal effects of the drug, they found that autism does not remain in a permanent state.

“This will indicate the cells were not frozen in this autistic state but they can be reverted back to normal,” Muotri said. “That points to a future drug screening platform where [one can test] thousands at the same time and will find one that’s very specific [and] very suitable for this conversion.”

Currently, the research group is using their autistic neuron model to screen more specific drugs to target neurons of people with autism.

Readers can contact Regina Ip at [email protected].