NEW YORK (360Dx) – A team led by researchers from Stemina Biomarker Discovery and the University of California, Davis' MIND Institute have identified metabolomic biomarkers that could be useful for diagnosing and guiding treatment in certain subsets of autism patients.
Detailed in a study published last week in Biological Psychiatry, the findings are the first published results from the Children's Autism Metabolome Project (CAMP), a 1,102-patient trial sponsored by Stemina with the goal of identifying metabolomic profiles linked to autism. The trial was funded with a $2.7 million grant from the National Institute of Mental Health and $3.8 million from the Nancy Lurie Marks Family Foundation.
The trial is intended to support the development of metabolomic-based autism tests by Stemina's neurological disorders division NeuropointDX. According to Elizabeth Donley, CEO of Stemina and an author on the study, the company plans to launch its first tests by the end of the year, offering them as laboratory-developed tests out of a CLIA facility.
Stemina was founded in 2007 to commercialize stem cell technology developed in the lab of Gabriela Cezar, then an assistant professor at the University of Wisconsin-Madison, and currently CEO of Panarea Partners, a healthcare and life sciences investment banking firm. The company's traditional focus has been using metabolomic analyses of stem cell-based models for toxicity screening of drug candidates, chemical compounds, and consumer products like cosmetics. Its autism program emerged from a project investigating the effects of a drug linked to increased incidence of autism when given to pregnant women.
In the Biological Psychiatry study, the researchers investigated whether alterations in the levels of amino acids and branched chain amino acids (BCAAs) in patient blood could help diagnose autism, an approach based on previous research from Madison, Wisconsin-based Stemina and other groups that indicated that "there may be amino acid dysregulation in autism," said David Amaral, professor of psychiatry at UC, Davis, and senior author on the study.
Amaral and his colleagues used LC-MS analysis on an Agilent G6490 triple quadrupole to quantify 31 amine-containing metabolites in a training setting consisting of 253 subjects with autism and 85 typically developing (TYP) subjects. They identified three amino acids — glutamine, glycine, and ornithine — that when measured as a ratio against the levels of three BCAAs (leucine, isoleucine, and valine) distinguished a subset of subjects with autism from TYP controls. In a test set consisting of 263 subjects with autism and 79 TYP controls, the researchers determined that the three AA/BCAA ratios could distinguish between the subjects with autism and the TYP controls with a sensitivity of 16.7 percent and specificity of 96.3 percent.
While at that level of performance the test would detect only around 17 percent of patients with autism, the results bolster the notion that metabolomic data can be useful in identifying patients at risk for the condition, said Amaral.
"This is the first of many papers in the future, and the presumption [is] — and we have evidence that this is the case — that there will be other metabolites indicative of other altered processes in autism that will identify other groups of kids," he said, adding that the researchers also hope the metabolomic data could eventually be used to guide treatments for the condition.
Stemina announced last year that it had identified six metabolomic subtypes of autism and earlier this year that it validated 12 subtypes that accounted for roughly 30 percent of children with autism.
Amaral said the patients identified by the amino acid measurements did not appear to cluster according to their clinical phenotype in any obvious ways.
"We don't see a specific pattern to their autism that is different from kids who don't have this diagnostic marker," he said, noting that this might be due to the fact that it was a relatively small group of patients distinguished by these markers.
"This is really a starting point for trying to define what is different about this group of kids from other kids with autism," Amaral said.
Despite Stemina's plans to launch a test based on the markers by the end of the year, it has yet to establish that they are in fact specific to autism, as opposed to developmental delay more generally.
"We really don't know [about the markers' specificity for autism] at this point," Amaral said, noting that logistical and financial challenges prevented the researchers from recruiting a control population consisting of children exhibiting developmental delays due to causes other than autism.
"In the fullness of time, I think we will be able to rule in or rule out other developmental disabilities that will have similar types of profiles," he said. "It wasn't that we hadn't thought about other developmental disabilities. It just wasn't, practically speaking, feasible in this first round of study."
Donley said she believed the test could still be of use to patients and physicians, suggesting that a positive result could help speed the process of diagnosing a child with autism, noting that in many cases families and pediatricians take a wait-and-see approach as opposed to referring a child to a specialist right away.
"If the physician and the family are concerned in the first instance and then there is a biological confirmation that there may be a problem with amino acid dysregulation, then that should lead to more confidence in referring [to a specialist]," she said.
Amaral suggested, as well, that it might become possible in the future to treat the observed amino acid imbalances. He added that while the Biological Psychiatry study does not provide evidence for the efficacy of such treatments, it does indicate amino acid imbalances could be a fruitful area of therapeutic research, which could foster more investigation.
"It lays out a potential strategy for moving forward with those groups of kids," he said.
Donley said the test will cost $1,000 if reimbursed by insurance and $750 for patients paying themselves.
She said the company is also working on a paper detailing a second set of markers identified in the CAMP study that it hopes to submit for publication before the end of the year.