Strength In Numbers
Hundreds of different genetic factors contribute to autism and likely a similar number of environmental factors. Each combines differently to affect an individual diagnosed with Autism Spectrum Disorder (ASD). The many different possible combinations of genomic and environmental “risk factors” results in many different individuals with ASD. Some have milder forms, others more severe, often accompanied by intellectual disability, and most have co-occurring mental health concerns, such as anxiety, depression and ADHD – a phenomenon known in the medical world as “heterogeneity.”
Large studies, with hundreds of participants, often through collaborations between different Universities and hospitals is often the only viable path for overcoming the challenge posed by heterogeneity. Autism genetic studies, for example, need to include a substantial amount of data from many thousands of individuals all across the spectrum in order to find meaningful underlying patterns. Genetic research is a natural fit for collaborative science, and the Center for Autism Research (CAR) is a member of several fruitful collaborations both within and outside of Children’s Hospital of Philadelphia (CHOP). Nationally, CAR is partnering with the Simons Foundation and more than 20 other research institutions across the country to enroll 50,000 families living with autism into the SPARK study to discover the genes contributing to autism. Nearing the three-year mark, CAR is exceeding expectations for enrollment, on the way to its goal of enrolling 10,000 individuals with ASD in the next 5 years. CAR was recently also awarded supplemental funding dedicated to ensure more members of ethnic and racial minorities are represented in genetic studies.
Within CHOP, CAR is partnering with the Department of Biomedical and Health Informatics and the Divisions of Neurology and Developmental and Behavioral Pediatrics to integrate genetic data into a biorepository for neurodevelopmental disabilities. As a key component of CHOP’s Autism Learning Health System, the biorepository is a data warehouse combining genetic data with key information from each person’s medical record data on their developmental and behavioral strengths and difficulties. This information-rich biorepository will accelerate autism research and its translation to new and improved treatments.
The end goal of all research collaborations, no matter the size, is “translation”- making sure the findings from rigorous, validated studies move quickly into clinical practice. This goal is at the heart of the Autism Learning Health System, and can be demonstrated by a recent genetic study. In 2017, CAR led research on 22q11.2 Deletion/ Duplication Syndrome, a genetic syndrome shared by many individuals with ASD. The resulting findings led to new screening recommendations and medical care for patients. Other genetic research at CHOP has led to a clinical trial that is testing the effectiveness of a medicine targeting the metabotropic glutamate receptors (mGluRs), to improve behavioral functioning, Past research has connected the mGluRs to learning, memory, and anxiety. Using this knowledge, researchers are now exploring medications that could improve social communication by targeting these receptors.
While much research is still needed, CAR is focused on translating its genetic findings into major advances in diagnosis and treatment for individuals with ASD. The Autism Learning Health System will combine genetics data with CAR’s current understanding of brain structure and function, behavior, ASD symptoms and developmental factors. The result will be a more integrated and robust understanding of how ASD works, and why it manifests differently from one person to the next. This understanding could revolutionize patient care for individuals with autism over the course of their lifetime, and provide a better foundation for continued research discovery.
”We’re not just looking at long-term outcomes, but also helping individuals with autism to have better quality of life now,” Robert Schultz, PhD, CAR’s scientific director, says. “Often times it’s less about finding a cure for autism, but instead discovering what an individual autism wants out of life and how we can help them achieve that.”
The Autism Learning Health System will combine patient data from clinical care and research studies to form an ongoing autism feedback loop. Scientific evidence will inform clinical practice, and clinical practice will new data for research and changes in clinical practice will be studied for their effectiveness. As this feedback loop cycles, answers will become clearer and research will become more refined.
“Ultimately, our goal at CAR is to merge data and clinical science, with clinical goals and skills in caring for families with ASD, to discover treatments and intervention which are meaningful to families and relevant for all,” says Dr. Schultz.