Researchers are using stem-cell technology to create brain tissue from the skin cells of people with autism. In doing so, they have overcome one of the greatest challenges in autism research.
“Up until now, researchers studying the molecular and cellular basis of autism could use only animal models or donated post-mortem brain tissue,” explains developmental pediatrician Paul Wang, Autism Speaks’ head of medical research. “Unfortunately, we have only a limited amount tissue available in brain banks such as Autism BrainNet. And research in animals – while very useful – will always have limitations in translating results to people.”
So-called brain organoids – live bits of brain tissue under an inch in diameter – represent an important new research tool to help overcome these limitations, comments Dr. Wang, who was not involved in the research published today.
The researchers focused on a distinct subgroup of people with autism – those with severe autism associated with an enlarged brain. Around one-fifth of those with severe autism share this characteristic. The researchers took skin cells from four study participants and, for comparison, from their unaffected family members. For each person, they converted the skin cells into pluripotent stem cells and then induced these to develop into a simple form of brain tissue – the brain organoid.
When the researchers analyzed the organoids from the participants with autism, they found unusual changes in the development of neurons (brain nerve cells). For example, their organoids overproduced inhibitory neurons, which quiet brain activity. This led to an imbalance of inhibitory neurons over the excitatory neurons that increase brain activity.
Of particular interest, they found that they could correct this imbalance by blocking the expression of a single gene. This, they suggest, could provide a promising direction for research aimed at developing medicines that might ease some types of autism.
"This study speaks to the importance of using human cells and using them in an assay that could bring a better understanding of the pathophysiology of autism and with that, possibly better treatments," says senior author Flora Vaccarino, professor of child psychiatry and neurobiology at the Yale School of Medicine.
The investigators are now building on their findings by isolating more of the genetic and epigenetic factors responsible for the neuron imbalances they discovered. (Also see “What is epigenetics, and what does it have to do with autism?”)
With current technology, human brain organoids reach only very early stages of brain development – equivalent to a few months after conception. Research aimed at extending their growth to later stages of brain development is underway.
Learn why post-mortem brain donation is so important to autism research – and how your family can register – at Autism BrainNet, an initiative of Autism Speaks and the Simon’s Foundation.