Excellence in clinical care and optimization of outcomes require innovative, rigorous scientific methods. CART scientists pursue groundbreaking investigations to uncover the underlying causes of ASD, identify markers of risk and prognosis, and advance the science of ASD treatments, including the areas outlined below. They then disseminate these findings to the community in order to promote best practices in clinical care and treatment and to help caregivers understand scientific discoveries.
Like all common human brain disorders, ASD has a strong genetic component. CART scientists have led the field of ASD genetics for more than a decade. Advances in genetics have changed the understanding of the underlying biological basis of ASD, and genetic testing has now become a standard part of the assessment for all children with ASD. More than half of all children with ASD have identifiable genetic variants that cause ASD, with genes that affect basic processes in brain development. By understanding the effects of genetic variants that cause ASD, physician-scientists can develop more specific and effective treatments that are tailored to the individual. This individualization of all aspects of diagnosis, treatment, and prevention is referred to as precision health. Implementing precision autism, delivering the right treatment, at the right time, to every patient, is a key goal of CART.
Brain mechanisms are analyzed at many levels. At the molecular or cellular level, the team creates stem-cell models based on genetic findings and study the effects of specific autism risk genes in scientific models. This is a major effort of several investigators in the center and in many collaborating laboratories in the surrounding UCLA neuroscience community. This allows researchers to connect molecular pathway dysfunction based on specific mutations to individual neuronal cells and circuits. The next step is to connect circuits to behavior, which also can be done in scientific models by manipulating these circuits to test treatments, etc. The next step is to discover how these models relate to human behavior and CART researchers use state-of-the-art brain imaging technologies to understand what is unique about the developing brain in individuals on the autism spectrum. Using functional magnetic resonance imaging (fMRI) to examine brain activity and the way the brain is wired, UCLA researchers are beginning to identify the brain mechanisms that lead to autism symptoms. Combining brain-based measures with genetic information enables investigators to determine how different risk factors for autism affect brain development and, ultimately, developmental outcome. MRI scans are a safe, noninvasive method that can be used to study individuals across the lifespan, includinag infants at high-risk for developing autism.
Early Markers of Risk
Informed by the knowledge of the genetic causes of ASD and the impact of these genes on early brain development, UCLA researchers are focused on identifying brain-based measures (biomarkers) of ASD that may be recognized well before developmental delays are seen. In contrast to behavior, which is observed subjectively, a biomarker represents an objective measurement of a specific biological process, such as brain waves, brain images, genetic markers, blood proteins, or eye movements. UCLA has a rich history of studying infants at high risk for ASD, with a focus on behavioral measures of social communication skills. Now, researchers are integrating those behavioral studies with innovative brain-imaging measures, such as MRI and electroencephalography (EEG), studying infants as early as one month of age. As UCLA investigators identify very early biological markers of risk for ASD, they can apply interventions early in development, with the ultimate goal of mitigating the burden or lessening the symptoms of ASD.
Through EEG, MRI, eye tracking, and other innovative tools, the CART team can image brain structure and function precisely, measuring patterns of connectivity and development throughout a person’s lifetime. Imaging studies can help scientists understand exactly how the brain is affected in ASD and how treatments can help to change brain networks and function. CART investigators are dedicated to developing brain-based biomarkers that will improve the measurement of outcomes in clinical trials and will help them identify meaningful subgroups within the autism spectrum who may respond better to specific treatments.
The knowledge gained about genetic mechanisms and their effects on brain function can now be used to inform the development and testing of new drugs for ASD using human stem-cell-based systems and high throughput drug screening. UCLA Investigators can make “autism in a dish” using new stem cell technology, and can use this system to screen for new compounds that can reverse the effects of the autism-causing mutations. This work provides a novel and unprecedented opportunity to develop therapies for individuals with ASD. Specific, focused, drug-therapy studies will enable the development of a scientific model based on genetic findings for ASD and support the integration of EEG and imaging as biomarkers of treatment response. Findings can identify existing drugs that were previously unidentified as promising potential treatments for core problems of ASD to be repurposed and studied.
Current treatments for ASD often produce only modest benefits. For example, despite community early intervention programs, as many as 25 to 30 percent of children with ASD never develop functional language. CART faculty includes preeminent international experts in ASD intervention who are focused on developing and enhancing interventions to address the major gaps in treatment. CART investigators have developed some of the best evidence-based interventions for ASD, including the earliest studies on Applied Behavior Analysis; social skills training programs, such as the UCLA Program for the Education and Enrichment of Relational Skills (PEERS), Children’s Friendship Training, modified cognitive behavioral protocols for treating anxiety and adaptive skill deficits, and the Joint Attention, Symbolic Play, Engagement, and Regulation (JASPER) therapy, proven to address core deficits in ASD in many rigorous studies. CART investigators helped direct clinical trials that led to the first FDA-approved medication for the treatment of severe behavioral problems in children with ASD. CART’s existing teams and staff are recognized as some of the most sophisticated intervention programs in the world.