MADISON, Wis.—Targeted toward discovering a way to diagnose autism in children younger than ever before, scientists at Stemina Biomarker Discovery and the UC Davis MIND Institute (Medical Investigation of Neurodevelopmental Disorders) at the University of California, Davis (UC Davis) conducted a study to compare the metabolomics signatures in the blood plasma of 4-to-6-year-olds with autism with those of typically developing children. The results, published in the November 2014 issue of PLOS One, indicates that an early-stage, blood-based test identified the autistic children with 81-percent accuracy.
Entitled “Research on the Metabolome of Children with Autism Spectrum Disorders,” the PLOS One study reports that researchers took blood samples over a 13-month period from 82 children—52 with autism spectrum disorder (ASD) and 30 without, then analyzed metabolites in the blood, trying to establish which of these small molecules signal autism. This method differs from other blood-based biomarker studies in the past few years that have tried to detect activity or expression of genes.
“We are very pleased with the result of this first study because it demonstrates that differences in the metabolism of children with ASD are profound enough to distinguish them from typically developing children,” Elizabeth Donley, Stemina co-founder and CEO, stated in a news release. “This will allow us to understand the individual metabolism of children with ASD in a way we never could before, leading to an earlier diagnosis and individualized treatment.”
ASD is a lifelong neurodevelopmental disorder characterized by social deficits, impaired verbal and nonverbal communication and repetitive movements or circumscribed interests. About one in 68 children has been identified with ASD, according to estimates from the U.S. Centers for Disease Control and Prevention.
The etiology of the vast majority of cases of ASD are unknown and their genetics have proven to be incredibly complex, according to the PLOS study. There is now widespread appreciation that there will be many causes of ASD with varying combinations of genetic and environmental risk factors at play.
Diagnosing the disorder as early as possible is crucial because studies have shown earlier treatment can boost the child’s cognitive and social skills, Donley said. The current standard for diagnosis is a series of behavioral tests conducted by experts, partly because scientists have yet to crack the code on the biology underpinning autism.
Donley believes the key to cracking that code lies within metabolomics, rather than focusing on biology or genetics.
“Our study provides proof of concept that the metabolism of children with autism is significantly different from that of typically developing children,” Donley tells DDNews. “Stemina’s metabolic approach to diagnosing autism will revolutionize diagnosis and treatment of ASD.”
Metabolomics not only provides an important piece of the puzzle, but it’s an opportunity to understand what is different about the metabolism of kids with autism from typically developing kids, and to treat the individual child in response to their own individual metabolism, she says.
The current average age of an autism diagnosis in the United States is 4.5 years, and Stemina is researching a diagnosis as early as age 2, paving the way for earlier screening and diagnosis to improve both therapy and outcome for patients and families.
Stemina has conducted two additional similar studies that achieved roughly the same results as the PLOS paper—another one in partnership with the UC Davis MIND Institute involving 278 patients, and a 210-patient study with the Arkansas Children’s Hospital Research Institute, Donley says. Stemina’s own autism test is still at least three years and one larger-scale study away from commercialization.
“Our work in autism began with a study that was conducted at the University of Wisconsin (UW) in the lab of Dr. Gabriela Cezar,” Donley relates. “She studied neural cells made from human embryonic stem cells dosed with valproic acid (VPA) as models of neurodevelopmental disruption using a metabolomics approach to discovering biomarkers associated with neurodevelopmental disruption.
“VPA is known to cause an increase in the incidence of autism in children exposed during gestation, and so Dr. Cezar hypothesized that she was creating a model of autism in the dish that might be seen in patients,” Donley explains. “Dr. Cezar next studied post-mortem brain tissue from the Autism Tissue Program and discovered some of the same pathways disrupted in the brains of children with autism as had been seen in neural cells in the dish.”
This was a UW study in collaboration with Stemina, which did the metabolomics study for Cezar’s lab, Donley says. Stemina then sought out sources of banked blood samples to develop a diagnostic test for autism.
The first generation of the diagnostic test will be delivered by Stemina and its partners as a laboratory-developed test, Donley says, adding, “Next generations will include a kit that could be used in pediatric clinics and specialty centers.”
While Stemina’s current autism test can identify about four-fifths of children with autism by analyzing 179 small molecules, the company’s goal is to identify more sub-signatures, of four to 11 biomarkers, that would give more information about the subtype of autism that a child has.
Stemina is trying to raise $5 million for a 1,500-patient study, Donley notes, adding she wants to begin enrolling patients next year, with the intention of commercializing the autism test by the end of 2017.
The funding drive has hit the ground running.
“We have a lead investor for our $5-million series B round,” Donley reports. The Nancy Lurie Marks Family Foundation has committed $2.3 million to fund the clinical study. Stemina has also applied for a $2.7-million Phase II SBIR grant to help support the study.
Stemina plans to initially commercialize the test by utilizing an FDA regulatory exception that allows companies to market laboratory-developed tests that they handle in-house, thus bypassing the typical FDA approval process. However, Stemina intends to eventually seek full FDA approval of the autism test.
Founded in 2006, Stemina has used its metabolomics technology to perform toxicity tests on compounds for drug developers, cosmetics and consumer products companies and the U.S. Environmental Protection Agency, among other customers. A blood test for autism would be the company’s first diagnostic product.
