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On The Frontlines of Autism Research: North Carolina Professors Study Early Detection, Treatment

On the Frontlines of Autism Research:  North Carolina Professors Study Early Detection, Treatment

From WBUR’s “Here and Now” | By Jeremy Hobson and Francesca Paris

Listen to the interview here

January 28, 2020

Researchers at the University of North Carolina at Chapel Hill say they can detect autism spectrum disorder before it manifests in some young children, and they’re even developing treatments for some of the conditions that go hand-in-hand with autism.  Professors Mark Zylka and Joe Piven work among more than two dozen scientists at UNC focused on autism spectrum disorder, and the National Institutes of Health have given the two more than $15 million combined in the last year alone. 

Autism is a developmental disorder that affects communication and behavior, with symptoms that can include repetitive behavior and difficulty interacting with other people.  

Piven has been able to detect autism in children as young as six months.  And Zylka has focused on treating a syndrome closely linked to autism with gene editing, research he says could open the door to a much broader slate of treatments. 

“There’s been a real revolution in the past 10 years in terms of our understanding of the genetic basis for autism,” says Zylka, who studies cell biology and physiology.  “This revolution has really been sparked by the rapidly reducing cost of sequencing human genomes.” 

Just this month, the largest genetic study of autism to date found more than 100 genes linked to the disorder. Those kinds of breakthroughs are stepping stones toward a better understanding of autism spectrum disorder, the researchers say.  

In addition to genetics, environmental factors including maternal health and prenatal exposure to air pollution play a role in the development of autism. The disorder is diagnosed in one in every 59 children in the United States, according to the Centers for Disease Control and Prevention. Two decades ago, the rate of diagnosis was just 1 in 150 children.

Piven, who studies psychiatry and pediatrics, says it’s hard to tell why the prevalence is increasing, though “better recognition and widening criteria” likely play a large role. But the increased prevalence has also generated enthusiasm for public and private funding, he says.

‘Earlier Is Better’

With that funding — including a $9.5 million grant from the NIH last year – Piven and his team have been looking at the brains of kids six to 12 months old.

He uses MRI brain-imaging to predict whether a child will develop autism, well before children turn two or three and start showing symptoms. The kids he’s studying have older siblings diagnosed with autism, so they run a much higher risk than the average child of developing it themselves — about a 20% likelihood.

But babies who later develop autism spectrum disorder “don’t look like they have autism in the first year of life,” he says. “That’s really quite amazing. And that window gives us an opportunity to think about early detection.”

While the infants don’t exhibit symptoms of autism, their brains look different from children who don’t develop the disorder, Piven says, including differences in “surface anatomy, surface area, convolutions on the surface.”

Those variations have allowed him to correctly identify eight out of 10 kids who would go on to develop autism in previous studies. He says that predictive tool could allow researchers to develop early interventions.

“Earlier is better,” he says. “As a rule of thumb in medicine, we treat things before they happen. … We are interested in high blood pressure because it leads to stroke, so we treat high blood pressure. And that’s a well-worn path.”

The interventions themselves are still an open question, he says, because researchers “haven’t been able to identify these children in infancy before.”

Turning Genes On And Off

One potential treatment, though, is gene editing.

That’s where Zylka comes in. His research, also funded by the NIH, involves mice instead of children for now. He’s trying to treat Angelman syndrome, a rare neurodevelopmental disorder often placed on the autism spectrum.

“These are children that are largely non-verbal,” Zylka says. “They have motor problems. It’s severely disabling.”

People with Angelman syndrome have a mutation in the maternal UBE3A gene. Normally, any given gene passed down from one parent doesn’t have to function perfectly because there’s a backup — the other parent’s gene.

But the paternal UBE3A gene is largely inactive, or “silenced.” That’s fine for most of us, but it means there’s no backup for a child born with a missing or defective maternal gene.

The paternal gene is “functional, but turned off,” Zylka says. “Using these new genome editing technologies like CRISPR-Cas, we’re going in and trying to turn on that dad’s copy of the gene.”

CRISPR has gained international acclaim for its promise in treating disease, but it has also generated controversy. A Chinese researcher who said he had illegally created the world’s first gene-edited babies was sentenced to prison last year.

But Zylka says his team has figured out ways to harness the tool’s power to treat Angelman syndrome without creating mutations that could be passed onto future generations.

So far, he’s been able to treat symptoms in mice, though not eradicate them — and he says the treatment has to be administered early in life to work properly. Eventually, he hopes to use CRISPR-Cas9 to edit the UBE3A genes of prenatal infants or newborns.

Zylka says he’s not finding a cure per se — an idea that many people with autism and advocates oppose — but trying to treat potentially devastating symptoms: Angelman syndrome can cause epilepsy and severe speech impairment.

“If you have a baby and at birth, they have some problem that surgery can correct, people are not going to neglect the surgery to fix the baby,” he says. “With genetics, we can actually pick these mutations up early, so … gene editing approaches could be used to treat early.”

He says this work could open the door to treating autism more broadly.

“CRISPR-Cas technology can be used to turn genes off or turn genes on,” Zylka says. “Since many cases of autism are due to loss of one copy, you still have a second copy that is functional. And so you could use an editing approach to turn on the functional copy to a higher level.”

Both Piven and Zylka say public funding from the NIH is a mainstay for their work. And they’re optimistic about the future of autism research, especially as more comes to light about the causes of autism syndrome disorder and the variations within that diagnosis.

“While we call this autism … these really aren’t [all] the same condition,” says Piven. “We just have these crude behavioral criteria. So I think we will pick away at the whole and start being very successful with some that have these more simple mechanisms. And others that are more complicated, we’ll have to tackle in other ways.”

Zylka says subtyping disorders might even let researchers come up with personalized treatment one day. But, he adds, we’re not there yet.

Find more information about recruitment for this study here.

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