Editor’s Note: Each year, 10,000 patients diagnosed with autism spectrum disorder (ASD) visit a wide range of clinical programs at Children’s Hospital of Philadelphia — including developmental pediatrics, child and adolescent psychiatry, neurology, psychology, speech and language therapy, clinical genetics, general pediatrics, and more. With this enormous patient base and broad sets of expertise across specialties, the Center for Autism Research (CAR) at CHOP offers a tremendous opportunity to conduct rigorous research with its ultimate aim being to improve care, quality of life and long-term outcomes for individuals with ASD. In this guest blog, CAR Director Robert Schultz, PhD, describes how CAR is building upon this remarkable strength with the support of patients and families, research collaborators, and partners like the Philadelphia Eagles, a National Football League team. The Eagles Autism Challenge, a one-day bike race, walk, and 5K being held May 19, is raising crucial funding to rapidly advance the work of outstanding physicians and researchers.
One person’s autism can look very different from the next. Autism is a multifaceted spectrum disorder, so its underlying mechanisms and outward manifestations vary widely, with important implications for optimal treatment strategies. And the knowledge we gain from research may apply to some types of autism but not easily translate to other types. Yet, one thing remains constant: The commitment of CAR’s experts, as well as clinical experts in the subspecialty practices that serve the great majority of this community; the individuals and families affected by ASD; and the support from our community to yield innovation in diagnosing autism, targeting therapies, and enabling a personalized medicine approach from infancy through adulthood.
Developing a precise understanding of the different varieties and manifestations of autism requires the ability to thoroughly evaluate ASD in thousands of people using the same procedures and research protocols. CHOP is one of the only places in the world that can do this. Gathering data and funding studies of the size and scope necessary to account for autism’s myriad expressions has been out of reach — until now.
Thanks to funds raised from initiatives like the Eagles Autism Challenge, CHOP is distinct nationally in our integration of research and clinical care. We have systematically expanded our clinical expertise, technology, and research infrastructure to allow for the collection of granular information on genomics, behavior, and brain science, in order to make fundamental discoveries in the era of precision medicine.
Understanding Genetics of Autism
Approximately 75 genes are known to significantly increase the risk of autism, and there are likely hundreds more left to be discovered. CHOP has been at the forefront of genomic science and has the ability to collect and analyze vast amounts of genomic data. The Eagles Charitable Foundation provided startup funding for CHOP to establish and build one of the world’s largest single-site biorepositories for autism.
One current clinical trial is based on discoveries from the Center for Applied Genomics at CHOP about a specific family of genes for ASD, called metabotropic glutamate receptors (mGluRs), which regulate various behavioral processes that influence learning, memory, attention, cognition, and sleep. Certain mGluRs present a “druggable target,” or a specific component of cellular machinery that could be modulated by a pharmaceutical, and CHOP researchers are testing medications targeting these receptors.
Precision Behavioral Evaluation
With the advent of body sensors, advanced computer vision, and natural language analytics, all behaviors that an expert clinician can observe may now be captured with technology, and used in artificial intelligence analytic frameworks to better understand autism and make extremely valuable real-world predictions. CAR’s international leadership in “digital phenotyping” is ushering in a new era for autism research, where encounters as brief as a few minutes can capture research grade information that is extremely precise and predictive of evaluations requiring more than 10 times the amount of time and resources. These data are particular important for developing more sensitive treatment outcome measures. Digital phenotyping, used in combination with genomics, promises to revolutionize clinical processes for diagnosis and ongoing management of care, including choosing the right treatment, at the right time, for the right person.
Our patent-pending “biometric sensor” technology can precisely measure subtle differences in tone of voice, facial expression, communicative gestures and heart rate, to precisely elucidate the behavioral phenotypes of autism. Using specialized algorithms developed by CHOP data scientists, this data can be combined with large scale genomic studies, neuroimaging data, and patient medical histories into a single stream to create a “digital fingerprint” of each individual along the ASD spectrum.
CHOP is a pioneer in using brain imaging to learn how autism develops in the brain over time. As CAR enters the third phase of a multi-site research collaboration called the Infant Brain Imaging Study (IBIS) funded by the National Institutes of Health, we are evolving new knowledge that we published in a series of studies last year. Our IBIS study team used magnetic resonance imaging to show how certain differences in the brain’s neuroanatomy and functional architecture during the first year of life could predict with 90 percent or greater accuracy who would develop autism by age 2. This is an extremely important finding because studies have shown that early intervention leads to better long-term outcomes for children with ASD.
In addition, our researchers are measuring the magnetic fields produced by electrical activity in the brain in response to sights, sounds, or textures to better understand differences in the way the brain processes signals in children with ASD. CHOP is one of the few hospitals in existence to be equipped with multiple magnetoencephalography (MEG) machines — including one of the only infant-specific MEGs in the world. The MEG device listens to the rapid electrical activity of nerve cells, literally hearing the brain communicating with itself. Subtle delays — only fractions of a second — have been discovered in some children with ASD by MEG Lab Director, Timothy Roberts, PhD, vice chair of research for the Department of Radiology, and his team at the Lurie Family Foundations MEG Imaging Center at CHOP. This finding is leading to research in both novel hearing modification devices and pharmaceuticals designed to speed up brain chatter, as well as basic studies of the neurobiological mechanisms underlying the spectrum of ASD.
By integrating brain imaging with our ability to collect and analyze genomic and technology-based behavioral information, we will be able to precisely map the three main domains of autism: genetics, the brain, and behavior — not just in a handful of patients in one study, but in thousands of patients who receive expert care at CHOP each year.