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Congratulations to our 2013 grant recipients.
3-Year Early Career Award:
Dr. Jill Locke: University of Pennsylvania
Multi-Site, Randomized, Controlled Implementation Trial of an Evidence-Based, Adult and Peer-Mediated Social Skills Intervention for Elementary School Children with Autism Spectrum Disorder
Co-funded with the FAR Fund
With the rising cost of educational services for children with autism and fiscal challenges that school districts face, it is imperative that cost-effective autism-related interventions are easily implemented and sustained in schools. Social impairment represents the most challenging core deficit of autism and greatly affects children’s school experiences; however, few evidence-based social skills programs have been translated into and sustained in schools because of the challenges that schools face when adapting and implementing evidence-based practices. This project will identify and address school-level challenges that interfere with the implementation of a promising social skills intervention that trains school staff to work with children with autism. If successful, this project will advance our understanding of implementing evidence-based social skills interventions in public schools and provide schools with a built-in mechanism to support their students.
Dr. Alexander Kolevzon: Icahn School of Medicine at Mount Sinai
Human Clinical Trial of IGF-1 in Children with Idiopathic ASD
A double-blind, randomized, placebo controlled, phase 2 human clinical trial of Insulin-Like Growth Factor-1 (IGF-1) in children with a genetic cause of autism (Phelan McDermid Syndrome) is currently underway at the Seaver Autism Center for Research and Treatment at Mount Sinai. That study builds on previous work in a mouse model system of Phelan McDermid Syndrome which showed that IGF-1 treatment reversed the effects of disrupted glutamate signaling associated with impaired learning and memory. This Treatment Grant will expand the current study to add a cohort of children with autism but without Phelan McDermid Syndrome. IGF-1 is a commercially available compound that is known to promote synaptic maturation and plasticity. It has already been shown to reverse behavioral and physiological deficits associated with Rett Syndrome in mouse models and preliminary results in children with Rett syndrome are promising. Results from this trial are expected to provide evidence that IGF-1 is safe, well tolerated, and efficacious in targeting core symptoms of autism in children without Phelan McDermid Syndrome because of the potential that the glutamate signaling pathway is relevant to diverse forms of autism.
Dr. Aimee Badeaux and Dr. Yang Shi: Boston Children's Hospital
Molecular Characterization of Autism Gene CHD8 in Shaping the Brain Epigenome
This research is aimed at understanding how the brain is wired during development and immediately after birth, with a focus on the function of a class of genes that are mutated in a significant number of patients with ASD. We think this type of gene responds to environmental cues to shape the brain; this could help explain how autism seems to arise from both genetic and environmental alterations. The knowledge gained from this research will illuminate common abnormalities in the young brain that cause autism, and will therefore guide the next generation of therapies to reverse these events and ameliorate autism symptoms.
Dr. Sara Schaafsma and Dr. Donald Pfaff: Rockefeller University
Sex-Specific Gene-Environment Interactions Underlying ASD
This project will investigate whether a gene-environment interaction can explain why boys are much more often affected by ASD than girls. This study uses a mouse model to investigate the interaction between immunological prenatal stress, a known predisposing environmental factor, with a mutation in a gene that is linked to ASD risk and whether this interaction is different for both sexes. It is hypothesized that males who are genetically vulnerable to develop ASD are more susceptible to the detrimental effects of prenatal immunological stress than genetically vulnerable girls. Knowledge about this sex-specific gene-environment may offer new avenues of enquiry into ASD, provide unique insights into its neurobiology, and therefore impact a variety of areas in ASD research. Identifying sex-specific interacting risk factors and thereby opening the possibility to decrease the chances of high-risk children for autism of developing the disorder would considerably impact the lives of these children and their families.
Dr. Teresa Tavassoli and Dr. Joseph Buxbaum: Icahn School of Medicine at Mount Sinai
Developing a Sensory Reactivity Composite Score for the New DSM-5
Sensory reactivity difficulties can be challenging for children with autism spectrum disorder and their families, making everyday activities, such as a trip to the supermarket, an impossible task. This project will look at how children with single gene and idiopathic (meaning unknown origin) forms of ASD react to sensory stimuli, e.g. touch and sound. Sensory reactivity will be measured using parent reports, observations and physiological measures, such as heart rate. Our aim is to identify the most robust ways to measure sensory reactivity in children with ASD, which can be used to guide diagnosis (sensory over-reactivity and under-reactivity as proposed for DSM-5) and sensory-based treatments. In addition, by including children with single gene forms of ASD this research can help to identify potential biomarkers for sensory over-and-under-reactivity. This research will also help to better understand the sensory world of children with ASD and can be used to design sensory-friendly environments.
Alexandra Bey and Dr. Yong-hui Jiang: Duke University
The Role of Shank3 in Neocortex Versus Striatum and the Pathophysiology of Autism
There are currently very limited options for treating patients with autism spectrum disorders due to poor understanding of the way the core behavioral deficits occur. In part, this is because the brain regions controlling the abnormal behaviors are unknown. This study will use a mouse model of autism, which allows us to very precisely disrupt the function of specific brain regions, to examine which regions control each category of ASD behavioral deficits. This will inform the development of new treatments that target specific brain regions tailored to the behavioral profile of the individual.
Ezzat Hashemi and Dr. Veronica Martinez-Cerdeno: University of California, Davis
Alteration of Dendrite and Spine Number and Morphology in Human Prefrontal Cortex of Autism
This project will analyze the cellular architecture of pyramidal neurons in the prefrontal cortex of postmortem human subjects with autism. Axons and dendrites transfer the electrical signals within the brain via the spines. These electrical signals, which are important in neural networks, are altered in autism. To determine the role of dendrites and spines in disrupted signaling, we will measure the length, volume and morphology of dendrites and spines using Golgi staining and Neurolucida tracing software. This study will further the understanding of micro-anatomical pathology and neural connections involved in signal transmission in autism, and therefore, it will take us a step closer to developing new treatments for autism and other neurodevelopmental disorders.
Jessie Northrup and Dr. Jana Iverson: University of Pittsburgh
Development of Vocal Coordination between Caregivers and Infants at Heightened Biological Risk for Autism Spectrum Disorder
This project will examine the timing of vocalizations in interactions between infant siblings of children with ASD and their caregivers throughout the first year of life in order to look for early warning signs of ASD and inform early interventions. From the first days of life, infant and caregiver interactions involve mutual give-and-take that is very important for infant development. One example of this is the way in which typically developing infants and their mothers adjust the timing of their vocalizations to coordinate with one another, much like two adults having a conversation. Coordination of the timing of vocal behavior with a partner involves a mix of attention, language development, and social engagement--and for that reason, it may be an ideal context in which to look for early symptoms of autism spectrum disorder. In addition, while a lot of research on ASD has focused on individual characteristics of the child, this study will help us understand infant behavior in the context of everyday social interaction, and will therefore have implications for early interventions focused on parent-child interaction.
Russell Port and Dr. Timothy Roberts: University of Pennsylvania
GABA and Gamma-band Activity: Biomarker for ASD?
The differences in brain activity that generate the symptoms of ASD are not understood, yet it is this very activity that is targeted by treatment. This research aims to directly study brain activity by measuring the magnetic signals generated by the brain as it responds to sound. Our research suggests that a certain kind of activity in the brain (gamma-band) is disrupted in children with ASD, and differences in the inhibitory neurochemical GABA is involved. By targeting the underlying biology, this research may allow us to determine which treatments are effective earlier and on an individual basis, and guide treatment development.