SACRAMENTO, Calif.—With an aim of launching a new biomarker test panel that could offer the first objective test leading to the earliest diagnosis of autism spectrum disorder (ASD) thus far, investigators at the MIND Institute at the University of California, Davis (UC Davis) and NeuroPointDX have identified a group of blood metabolites that could help detect some children with ASD as young as 18 months old.
The research was published Sept. 6 in the journal Biological Psychiatry, as part of the 1,100 subject Children’s Autism Metabolome Project (CAMP), reportedly the largest ASD metabolism study ever attempted. The article reports on how investigators at the UC Davis MIND Institute and NeuroPointDX, a division of Stemina Biomarker Discovery, have identified specific alterations in metabolic profiles that can detect sizable subsets of individuals with autism.
In this latest study, the research team compared blood metabolites—specifically, amino acids—in 516 children with ASD and 164 children showing typical development.
“With this panel of alterations in amino acid metabolism, we can detect about 17 percent of kids with ASD,” says David G. Amaral, founding director of research at the MIND Institute and senior author on the journal paper. “This is the first of hopefully many panels that will identify other subsets of kids with autism.”
“[Though] a 17 percent subgroup may seem small, it is actually quite significant,” Amaral says. “ASD encompasses a complex array of symptoms, and no one expected to find a single group of markers that would diagnose all subsets. Rather, researchers hope to create a number of metabolomic assays that cover all variations.”
With no biomarker tests for ASD currently existing, children are diagnosed based on their altered behaviors, which may not become evident until they are 2 to 4 years old, Amaral says. Then families often must wait over a year or more for an appointment with a specialist, delaying a diagnosis even further.
The standard of care for children diagnosed with ASD is one of intensive behavioral therapy generally based on applied behavior analysis (ABA) therapy, which is rooted in the scientific study of the principles of learning and behavior, Amaral tells DDNews, adding that ABA therapy can improve outcomes for children with ASD.
However, “the outcome for each child is very individual,” Amaral notes. “Improvements in cognitive function (increase in IQ) and reduction in autism symptoms have been demonstrated, but the earlier the therapy is applied, the better the outcome.”
CAMP researchers believe the answer lies in the metabolome—the molecules that remain after larger molecules have been broken down (metabolized). Metabolomics has the advantage of monitoring both genetic and environmental contributions to the development of autism.
“By the time you’re getting to metabolomics, you’re looking at how the body is working, not just the genes it has,” Amaral explains. “The team hopes to use these and other CAMP findings to accelerate a diagnosis and move kids into intensive behavioral therapy at an earlier age.
“It is unlikely that a single marker will detect all autism,” he says. “This paper demonstrates that alterations in metabolic profiles can detect sizable subsets of individuals with autism. The hope is, we will be able to generate a panel of biomarkers that will detect a large proportion of people at risk. Moreover, this approach highlights metabolic pathways that may be targets of intervention.”
In addition to enabling an earlier ASD diagnosis, this research also could help generate targeted interventions for specific ASD groups such as phenylketonuria (PKU) as a possible template, he says. PKU is a rare disease in which the amino acid phenylalanine builds up, causing brain damage.
“With just a simple dietary modification, a child can move from being profoundly disabled to one who lives a reasonably normal life,” said Amaral. “That’s the hope with autism as well.”
The CAMP researchers will continue to validate these results while simultaneously investigating other metabotypes, he adds.
“I’m optimistic this [study] is not a one-off,” Amaral comments. “There are going to be other panels that can detect other groups of kids with ASD.”
Autism spectrum disorder is made up of a diverse set of neurodevelopmental disorders that arise from differences in underlying genetic, metabolic and environmental factors, resulting in a spectrum of cognitive, behavioral and biological profiles. ASD is marked by communication, behavioral and social difficulties.
Elizabeth Donley, NeuroPointDX’s CEO and a co-author of the journal publication, says, “Using a metabolomics approach to detect ASD risk holds substantial promise for the identification of objective ASD biomarkers because metabolism is sensitive to interactions among the genome, gastrointestinal microbiome, diet and environmental factors that all contribute to an individual’s unique metabolic signature. Metabolic testing can provide important biochemical signatures that help identify disruptions in biological processes that underlie an individual’s ASD.”