Testing and Refining Biomarkers to Support Intervention Research for Children with Autism
Autism spectrum disorder (ASD) affects early brain development with signs and symptoms emerging in the first two years of life. People with ASD have difficulty with social communication and interaction, restricted interests, and repetitive behaviors. Autism is known as a “spectrum” disorder because there is wide variation in the type and severity of symptoms people experience. Because of this symptom variation, testing new treatments can be complicated. There is a need for objective measures—biomarkers—that can separate individuals with ASD into subgroups for clinical trials, leading to more predictive and personalized treatment.
The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) was established in 2015 to address this need. The goal of the multisite study was to test and refine a set of biomarkers that could be used as reliable, objective measures of variation in social impairment in ASD. The study enrolled children ages 6 to 11 with and without ASD and evaluated the potential use of electroencephalogram (EEG), used for measuring brain activity, and an eye tracking technology, used to measure social-visual attention, as potential biomarkers that could be used in studies to identify subgroups of participants with ASD. The researchers also collected clinician and caregiver assessments and blood samples from participants with ASD and their parents. Ultimately, the researchers wanted to test and refine these objective measures of social impairment for use in clinical trials, which could help define which individuals with ASD would best respond to particular treatments. Primary analyses of the data were completed in June 2020.
In the study, one EEG biomarker called the N170, that reflects the neural processing of faces, showed promising performance. Based on the results, the researchers submitted a Letter of Intent for the biomarker to the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research Biomarker Qualification Program. In May 2019, the N170 became the first biomarker for a neurodevelopmental disorder or psychiatric condition accepted into that program. Another promising biomarker, an eye tracking composite measure that quantifies visual attention to human faces, was subsequently submitted to the FDA biomarker program, and in March 2020 was accepted as well.
The ABC-CT project, led by James McPartland, Ph.D., of Yale University, was recently awarded funding to continue the work of this study. This second stage of the project will have multiple components including:
- A follow-up study of the original cohort to examine the longer-term stability of these measures, with re-administration of the biomarkers and clinical tests.
- The same study with a new cohort of children to see if the original findings can be replicated and confirmed.
- A feasibility study, looking at these same EEG and eye tracking measures in children ages 3 to 5, both with and without ASD.
- A continuation of blood sample collection and data sharing.
The project is supported by a cooperative agreement mechanism and co-funded by the National Institute of Mental Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, and the National Institute on Deafness and Other Communication Disorders. Research sites include Yale University; Duke University; the University of California, Los Angeles; the University of Washington, Seattle; Seattle Children’s Research Institute; Boston Children’s Hospital; and the University of Alabama at Birmingham.
Clinical trial number
NCT02996669 (for first phase)