2007 Physician/Investigator Beginning Autism Research (PIBAR)
2007 Physician/Investigator Beginning Autism Research (PIBAR)
2007 Augmentation Grants
2007 Innovative Technology for Autism (ITA) Grants
2007 Mentor Based Fellowships
2007 Opportunity and Bridge Grants
2007 Special Co-Funding with Dana Foundation
Naama Barnea-Goraly,M.D.
Stanford University
$200,000 for 2 years
Investigation of cortical-folding complexity in children with autism, their autism-discordant siblings, and controls
Several structural brain abnormalities have been associated with autism, but none have been consistently replicated and no single abnormality is seen in all persons with autism. A potential factor contributing to these inconsistencies is the inherent difficulty in controlling for genetic and environmental variables that influence brain development.
To overcome this difficulty, Dr. Barnea-Goraly will compare brain structure in siblings discordant for autism (sibling pairs in which one has autism and the other does not). This design minimizes genetic and environmental differences that could influence brain morphology. The study will use an innovative analysis of brain-surface complexity in individuals with autism, their non-autistic siblings, and in control subjects to examine the relationship between brain structure and autism. The study will also assess brain-surface complexity in very young subjects with autism (23-43 months of age) as compared to age- and gender-matched control subjects. This very young population will allow investigation of brain structure at the earliest ages in which autism diagnosis is possible. In addition, measures of brain-surface complexity will be compared to behavioral features of subjects with autism.
What this means for people with autism: This study will help specify the brain regions most highly associated with autism, and how these regions develop throughout childhood. A better understanding of the neurobiological underpinning of autism will allow for the identification of meaningful subgroups of individuals with this condition and the development of more targeted treatments for cognitive and behavioral symptoms.
Stephen Bent, M.D.
University of California, San Francisco
$300,000 for 3 years
Safety and efficacy of complementary and alternative medicine for Autism Spectrum Disorders
Recent surveys have found that most families treat their affected children with one or more forms of complementary and alternative medicine (CAM) in an effort to improve outcomes. To date, studies that rigorously evaluate the scientific evidence for safety and efficacy have been published for only four CAM therapies for ASD, and there is no readily accessible source of information to inform families about the potential risks and benefits of over 50 reported CAM therapies used in this disorder.
This project will determine and report on the safety and efficacy of CAM therapies in three ways. First, a survey will be conducted of parental perceptions of efficacy, cost, and time devoted to each intervention. Second, systematic literature reviews will evaluate all prior published evidence for each CAM therapy and make the information available on an open-access website to families and providers. Third, pilot studies will be initiated to more clearly determine the potential mechanism of action of the most promising CAM therapies.
What this means for people with autism: Any CAM treatment scientifically proven beneficial can immediately be adopted to help those with ASD. Likewise, when therapies are found to be ineffective, families and providers can direct their time and financial resources toward other treatments. (Co-sponsor: The Emch Foundation)
Eric Morrow, M.D., Ph.D.
Massachusetts General Hospital
$300,000 for 3 years
Translational Genetic Studies in Familial Autism Spectrum Disorders
Finding a genetic mutation that is shared in many cases of autism has been elusive, and is partly due to the genotypic heterogeneity among affected individuals. To circumvent this, it would be useful to look at people who have decreased variation in their genome, such as those whose parents are cousins. These “consanguineous” individuals are homozygous for many alleles, and searching these homozygous regions in people who are also affected by autism can expedite the search for the autism-related genes.
Dr. Morrow's project represents the first systematic application of homozygosity mapping to identify genes involved in autism. It will make use of a consanguineous patient population available from the International Autism Homozygosity Mapping Collaborative (IAMHC). The study will focus on finding mutations that are gene deletions. Deletions that are shared by this patient population will be candidate gene mutations related to autism. These genes will be further assessed in a second, more genetically variable patient group which consists of a large collection of North American families and patients with autism from the Autism Genetics Resource Exchange (AGRE). The principal tool for both of these analyses will be high-density genotyping microarrays ("gene chips").
What this means for people with autism: The identification of autism susceptibility genes through this line of research will contribute to a deeper understanding of the disorder, may lead to genetic diagnostic subtyping, earlier diagnosis, and genotype-based predictions of treatment response and outcome.
Craig Powell, M.D., Ph.D.
University of Texas Southwestern Medical Center
$300,000 for 3 years
Animal models of autism: pathogenesis and treatment
Mutations in the neuroligin gene have been implicated in a subset of autism cases. Neuroligin is a cell-adhesion molecule found at synapses, which are connection points between neurons. Neuroligin molecules form a bridge across these synaptic connections by binding to a molecule called neurexin. Thus, mutations in neuroligin could disrupt neural connectivity.
This research project will introduce the autism-related neuroligin mutation in mice. These mice will have the very same genetic cause of autism as a subset of autism patients. Experiments will test these mice for behavioral and neural abnormalities that may be related to autism. Preliminary data suggest that these mice exhibit specific deficits in social interaction, yet also exceed normal mice on one measure of learning and memory function. In addition to behavioral analyses, the project will also assess neural function in these mice, particularly at the level of the synapse.
What this means for people with autism: These studies will create a novel animal model of autism based on known human genetic causes of the disorder. Discovering how this genetic abnormality leads to changes in the biology (that result in the behavioral symptoms in this model) can identify potential new targets for disease treatment.
Stanford University
$200,000 for 2 years
Investigation of cortical-folding complexity in children with autism, their autism-discordant siblings, and controls
Several structural brain abnormalities have been associated with autism, but none have been consistently replicated and no single abnormality is seen in all persons with autism. A potential factor contributing to these inconsistencies is the inherent difficulty in controlling for genetic and environmental variables that influence brain development.
To overcome this difficulty, Dr. Barnea-Goraly will compare brain structure in siblings discordant for autism (sibling pairs in which one has autism and the other does not). This design minimizes genetic and environmental differences that could influence brain morphology. The study will use an innovative analysis of brain-surface complexity in individuals with autism, their non-autistic siblings, and in control subjects to examine the relationship between brain structure and autism. The study will also assess brain-surface complexity in very young subjects with autism (23-43 months of age) as compared to age- and gender-matched control subjects. This very young population will allow investigation of brain structure at the earliest ages in which autism diagnosis is possible. In addition, measures of brain-surface complexity will be compared to behavioral features of subjects with autism.
What this means for people with autism: This study will help specify the brain regions most highly associated with autism, and how these regions develop throughout childhood. A better understanding of the neurobiological underpinning of autism will allow for the identification of meaningful subgroups of individuals with this condition and the development of more targeted treatments for cognitive and behavioral symptoms.
Stephen Bent, M.D.
University of California, San Francisco
$300,000 for 3 years
Safety and efficacy of complementary and alternative medicine for Autism Spectrum Disorders
Recent surveys have found that most families treat their affected children with one or more forms of complementary and alternative medicine (CAM) in an effort to improve outcomes. To date, studies that rigorously evaluate the scientific evidence for safety and efficacy have been published for only four CAM therapies for ASD, and there is no readily accessible source of information to inform families about the potential risks and benefits of over 50 reported CAM therapies used in this disorder.
This project will determine and report on the safety and efficacy of CAM therapies in three ways. First, a survey will be conducted of parental perceptions of efficacy, cost, and time devoted to each intervention. Second, systematic literature reviews will evaluate all prior published evidence for each CAM therapy and make the information available on an open-access website to families and providers. Third, pilot studies will be initiated to more clearly determine the potential mechanism of action of the most promising CAM therapies.
What this means for people with autism: Any CAM treatment scientifically proven beneficial can immediately be adopted to help those with ASD. Likewise, when therapies are found to be ineffective, families and providers can direct their time and financial resources toward other treatments. (Co-sponsor: The Emch Foundation)
Eric Morrow, M.D., Ph.D.
Massachusetts General Hospital
$300,000 for 3 years
Translational Genetic Studies in Familial Autism Spectrum Disorders
Finding a genetic mutation that is shared in many cases of autism has been elusive, and is partly due to the genotypic heterogeneity among affected individuals. To circumvent this, it would be useful to look at people who have decreased variation in their genome, such as those whose parents are cousins. These “consanguineous” individuals are homozygous for many alleles, and searching these homozygous regions in people who are also affected by autism can expedite the search for the autism-related genes.
Dr. Morrow's project represents the first systematic application of homozygosity mapping to identify genes involved in autism. It will make use of a consanguineous patient population available from the International Autism Homozygosity Mapping Collaborative (IAMHC). The study will focus on finding mutations that are gene deletions. Deletions that are shared by this patient population will be candidate gene mutations related to autism. These genes will be further assessed in a second, more genetically variable patient group which consists of a large collection of North American families and patients with autism from the Autism Genetics Resource Exchange (AGRE). The principal tool for both of these analyses will be high-density genotyping microarrays ("gene chips").
What this means for people with autism: The identification of autism susceptibility genes through this line of research will contribute to a deeper understanding of the disorder, may lead to genetic diagnostic subtyping, earlier diagnosis, and genotype-based predictions of treatment response and outcome.
Craig Powell, M.D., Ph.D.
University of Texas Southwestern Medical Center
$300,000 for 3 years
Animal models of autism: pathogenesis and treatment
Mutations in the neuroligin gene have been implicated in a subset of autism cases. Neuroligin is a cell-adhesion molecule found at synapses, which are connection points between neurons. Neuroligin molecules form a bridge across these synaptic connections by binding to a molecule called neurexin. Thus, mutations in neuroligin could disrupt neural connectivity.
This research project will introduce the autism-related neuroligin mutation in mice. These mice will have the very same genetic cause of autism as a subset of autism patients. Experiments will test these mice for behavioral and neural abnormalities that may be related to autism. Preliminary data suggest that these mice exhibit specific deficits in social interaction, yet also exceed normal mice on one measure of learning and memory function. In addition to behavioral analyses, the project will also assess neural function in these mice, particularly at the level of the synapse.
What this means for people with autism: These studies will create a novel animal model of autism based on known human genetic causes of the disorder. Discovering how this genetic abnormality leads to changes in the biology (that result in the behavioral symptoms in this model) can identify potential new targets for disease treatment.
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