Upstate seeking participants for revolutionary autism study
By Sarah Hall
Editor
For Olivia Colabufo, learning her son had autism was something of a relief.
“For a lot of families of kids with autism, they’re afraid of the diagnosis,” said Colabufo, of Camillus, whose 3-and-a-half-year-old son Jackson was diagnosed last year. “They’re afraid of the word. The truth is that having that diagnosis was such a door-opener for me. Jackson has qualified for more services and more help and has made so much more progress because of that label. It’s scary in a prognosis type of way, but it’s opening so many doors to get him the help he needs.”
Research has shown that early behavioral intervention for kids with autism provides measurable benefits. One study published in the Journal of the American Academy of Child & Adolescent Psychiatry noted that certain intervention models resulted in normalized brain activity in toddlers with autism, as well as greater increases in IQ, language and adaptive behavior than children of the same age group who did not participate in the same therapy.
And the earlier services are provided, the better the outcome. That’s why early diagnosis is crucial — and why SUNY Upstate Medical University is working on a pioneering research study that could change the way autism is identified.
The study, which is currently seeking participants ages 2 to 6, measures for microRNA in the saliva of young children. The director of the study, Upstate Associate Professor Dr. Frank Middleton, hypothesizes that microRNAs impact brain activity, and finding microRNA particles with higher levels in children with autism can prove to be a diagnostic tool at an earlier age, as well as provide a better understanding of how the brain of someone with autism works.
“The vast majority of kids on the spectrum, there is no known cause,” said Middleton, who noted that only about 10 percent of autism cases could be traced to a genetic cause. “Therefore, we look in the epigenetic environment. And what epigenetics really means is something that happens to the products of your genome, but it doesn’t directly change the sequence of your genome. So I think it is pretty revolutionary.”
The science behind the study
So what is microRNA? Discovered in 1993, microRNAs are small non-coding strands of ribonucleic acid (RNA) involved in the regulation of gene expression. RNA is responsible for making proteins to respond to any need in the body. Meanwhile, each microRNA can block the expression of dozens to hundreds of those distinct proteins. Determining which microRNAs are in a given biological sample can indicate which proteins are being blocked.
“We know that microRNAs are extremely relevant to every biological function now,” Middleton said. “You can’t actually make an embryo unless you have actions of microRNAs right from the beginning.”
MicroRNA is present in all biofluids, but for the purposes of the study at Upstate, Middleton and his research partners, Dr. Steven Hicks at Penn State Milton S. Hershey Medical Center in Hershey, Pennsylvania, and Quadrant Biosciences are focusing on saliva.
“Saliva actually has been most wired-in to the nervous system,” Middleton said. “It’s the same reason that we enjoy the foods that we eat and drink. We have all these nerves that connect the brain to the mouth, and they run in both directions. And the microRNAs that are made in the brain can travel into the mouth down these nerve paths.”
This research is the continuation of a pilot study conducted last year that examined about two dozen children with autism and about 21 neurotypical kids. The pilot provided enough information and encouragement for the team to pursue the full study, for which Upstate is recruiting at least 200 children on the spectrum ages 2 to 6. Researchers are also recruiting neurotypical kids to act as a control group.
“We do full workups on all of them,” Middleton said. “We evaluate their behavior, and we measure their saliva for the presence of microRNA difference.”
More play than work
The study itself is simple: parent and child head to Upstate, where they will be provided with free parking. Children are given a cheek swab to collect the saliva sample. The process is painless, according to Cynthia Dowd Greene, executive vice president of operations for Quadrant Biosciences, Inc. The neuroscience biotech company, a START-UP NY company, located on the Upstate campus, was awarded funding for the study from the National Institute of Health.
“It’s very short and very quick and not threatening and not blood—no blood drawn,” Dowd Greene said.
Kids are then given the Autism Diagnostic Observation Schedule (ADOS), a diagnostic test that uses structured and semi-structured tasks, mostly play-based, involving interaction between the child being tested and an examiner.
“It’s a game. It’s interacting with the person conducting the test, and it’s playing with toys,” Dowd Greene said. “It’s not threatening.”
The test is conducted by staff with experience working with children with autism. Meanwhile, their parents answer questions regarding their health and habits. The whole process takes one hour. At the end, the family receives a $25 gift card.
Olivia Colabufo learned of the study through the Margaret L. Williams Developmental Evaluation Center at Upstate, where Jackson was diagnosed.
“There’s a survey that asks about your child. It asks really specific questions — about what they eat, how they act, how they speak,” she said. “While you’re there, they do a play evaluation. It seemed like they were just playing with Jackson.”
Colabufo also noted that the researchers were extremely accommodating.
“He took part in the swab part of the study last year when he was 2 and a half, and he refused to play with the person, and they didn’t make him do it. They were very good about it,” she said. “When we went back this year, they asked if they could try again, and he did it. They were really great — overly accommodating to parents and kids. They understand it’s not easy and that these are kids with disabilities. There’s no judgment. They go out of their way to make you comfortable and to understand that these kids might have a hard time.”
Earlier detection, earlier intervention
While these tests won’t lead to a cure for autism — there is no cure for the disorder — earlier diagnosis will allow parents to seek out services for their children as soon as possible.
“The word is early intervention,” Middleton said.
Current screening for autism involves a brief test with the child’s pediatrician during his or her 18- and 24-month well-child visits. Children are administered a test known as the Modified Checklist for Autism in Toddlers (M-CHAT), which asks about the child’s play patterns, social interactions, responses to stimuli, speech and other developmental milestones. If the test indicates a high risk for autism spectrum disorder, the child will be referred to a developmental specialist. However, due to the lack of specialists, the wait for actual intervention is about a year.
“That’s a year lost, at a critical time in development,” Middleton said. “It’s so much that goes on. Just think of every toddler you’ve known or seen between ages 2 and 3.”
The test being studied at Upstate seeks to streamline the diagnostic process.
“We think this test could function like a rapid strep test,” Middleton said. “In our data, in our hands so far, it’s about as accurate as a rapid strep test. We’re getting more than 85 percent accuracy.”
While it won’t eliminate the backlog for services, it will allow parents to start seeking them earlier.
“What we’re proposing is that it won’t take that year and a half to get that diagnosis,” Dowd Greene said. “You have your saliva tested, and therefore the diagnosis comes much quicker, in a couple of weeks.”
“If we have the opportunity to do a simple molecular test that can facilitate a kid getting services sooner, in potentially having a better outcome than if they went without those services, then it’s sort of a no-brainer for me,” Middleton said. “We have to do things like this.”
Middleton stressed that the microRNA test shouldn’t be used on its own but as a tool in an arsenal of diagnostic tests.
“By itself, just measuring the microRNAs, we wouldn’t recommend that,” he said. “We recommend that the child also have other observations entered into the record. We’re trying to come up with a really robust evaluation of the saliva test, compared to what is considered gold standard behavioral assessment.”
In order to complete that evaluation, Middleton and his team need research subjects. While two autism centers in Schenectady and Erie participated, and samples have been sent from as far away as Los Angeles, Upstate hopes to gather more from the Syracuse area. Dowd Greene said participation in the study allows families to not only be a part of “novel research,” but also to make a difference.
“It may not make a difference for their children, their child, but it may make a difference for lots of families with autism. And as anyone knows, when you experience it, it’s a tough road to go down,” she said. “And anything to make that road easier and faster is going to benefit families.”
Colabufo agreed.
“For me, being able to have a definitive answer about whether or not your child has autism — People have to wait a really long time,” she said. “If you can swab a newborn and know there’s a chance, you can start early intervention so much earlier. That’s [going to have] such a huge impact for so many other families.”
For more information about the study or to sign up, visit upstate.edu/autismstudy.
