Research Funded: Winter 2008
13 projects funded in two categories: Pilot Study and Basic and Clinical Research Grants
13 projects funded in two categories: Pilot Study and Basic and Clinical Research Grants
“We are extremely pleased to announce a new set of pilot study and basic and clinical research grants,” said Geri Dawson, Ph.D., Autism Speaks Chief Science Officer. “These studies are all ground-breaking. Some will explore ways to help people with autism function better in social situations. Others will explore new potential environmental risk factors. Several are using autism genetic findings to help lay the foundation for developing drug treatments for autism.”
Pilot Study Grants
Autism Speaks will award $893,265 in new funding commitments for eight pilot study grants. These grants draw new investigators into the field of autism research and allow researchers to collect preliminary data to demonstrate the plausibility of an innovative area of exploration.
Several of the grants selected for funding directly address current issues of parent concern. As a large number of children with autism are transitioning into adolescence, their ability to navigate safely in our society without prejudice is of foremost concern for all. One pilot study (Elizabeth Kelley, Ph.D., Queen's Univ.) will address social difficulties in adolescents with Asperger's or high-functioning autism by identifying the behavioral factors that can lead to the “bullying” or victimization of these children by their peers. The study has the potential to identify better ways for parents and teachers to intervene in order to promote social inclusion.
Another pilot study (Avi Reichenberg, Ph.D., Institute of Psychiatry, King's College London) will examine a potential risk factor for autism, assisted reproductive treatment (such as in vitro fertilization), that has raised concern. Researchers will examine population-based data covering the past two decades to determine whether there is a link between the use of assisted reproductive treatment and risk for autism.
Sleep problems are another common concern voiced by parents. However, assessing such sleep problems is challenging. One group of researchers (Gregory Barnes, M.D. Ph.D., Vanderbilt Univ.) will examine whether epilepsy-associated patterns of brain activity during sleep can be linked to behavioral problems in children with autism while they are awake. Results from this study will help identify some of the causes of sleep disruption in autism and will allow clinicians to better plan treatments to help children sleep well at night and function better during the day.
Two researchers will conduct separate large-scale analyses of genetic risk factors. One study (Kathleen Millen, Ph.D., Univ. of Chicago) will explore a set of genes involved in the development of the cerebellum, a region of the brain that is often anatomically abnormal in people with autism. The researchers hope that focusing on genes involved in cerebellar development will provide clues to the genetic causes of autism. In another study (Maja Bucan, Ph.D., Univ. of Pennsylvania), researchers will use very new bioinformatics approaches to examine whether several autism susceptibility genes are involved in a molecular pathways. This work can help translate our knowledge about genes into an understanding of how those genes may interact and affect the biochemistry of the body. Both of these projects should help scientists better understand how multiple different genes converge on common biochemical pathways that lead to autism. Such studies are of great relevance to treatment because research in other disorders has shown us that targeting biochemical pathways, as opposed to the function of an individual gene, may help inform useful treatment strategies.
Two other projects will focus closely on the biology of a particular set of genes, called the neurexins and neuroligins. Mutations in these genes have been found some individuals with autism. The proteins made by these genes are thought to be involved in the function of synapses, the connections between neurons. One pilot study (Davide Comoletti, Ph.D., Univ. of California San Diego) will determine how these mutations affect the ability of the proteins to bind to each other. This knowledge may lead to an opportunity to correct the abnormal interaction. In the second study (Linda Restifo, M.D. Ph.D., Univ. of Arizona), researchers will develop a new automated method to study the functions of neuroligins and neurexins. They will use neurons engineered to make the mutated proteins and test them in a high-throughput screen of FDA-approved drugs. This will evaluate the ability of candidate drugs to reverse the effects of these autism-associated mutations. These neurons will also be tested for their sensitivity to thimerosal.
Finally, a new animal model will be created to focus on the properties of neurons expressing oxytocin and vasopressin, two neuropeptides involved in normal social behavior (Shlomo Wagner, Ph.D., Haifa University). The precise network of neurons that utilize these peptides is not known, which has greatly hindered progress in understanding their exact function. The researchers will now develop lines of genetically engineered mice that can be used to identify, observe, and manipulate these neurons. This work may provide a foundation for parallel research into if and how these networks are disturbed in people with autism, and whether modulation of the peptides may serve as a viable treatment option.
For a complete listing of Pilot grant abstracts, click here.
Basic and Clinical Grants
Autism Speaks will award $1,523,172 in new funding commitments for five basic and clinical research studies. Topics selected for funding include potential prenatal factors that confer a risk of autism, the identification of subtypes of sleep and behavioral problems in children with autism, and how neural connectivity is affected in the brains of individuals with autism.
Two studies will examine prenatal environmental factors that may cause neurodevelopmental problems in the fetus, contributing to a higher risk of autism. One study (Richard Ebstein, Ph.D., Hebrew Univ.) will take an epidemiological approach to examining the role of drugs that are commonly administered to pregnant women to either prevent or induce labor. The other study (Theo Palmer, Ph.D., Stanford Univ.) will investigate how activation of the maternal immune system during pregnancy affects fetal development, focusing on the effects of maternal infections on placental functioning. If infections perturb the supply of blood and oxygen to the developing fetus, fetal brain development could be affected. These studies have the potential to suggest new preventative measures that can be taken during pregnancy.
Another study (Susan Mayes, Ph.D., Penn State College of Medicine) will conduct a large-scale analysis of the associations between sleep problems and behavior in children with autism. Determining whether any particular sleep disturbances are correlated with specific learning, mood, or behavioral problems will not only be invaluable in developing strategies to improve behavior in children with autism, it will offer an opportunity to immediately have a positive impact on the quality of life for families.
Finally, an emerging theory regarding the biological basis of autism is that the disorder results from changes in neural connectivity in the developing brain. Using recently developed non-invasive techniques to measure brain activity and the communication between different brain regions, two projects will study neural connectivity. In a very unusual opportunity to examine data collected on the same subjects over the time span of a decade, one imaging study (Natalia Kleinhans, Ph.D., Univ. of Washington) will use a longitudinal approach to draw a relationship between altered functional brain connectivity in adolescents at age 15 and atypical head growth that occurred much earlier during their infancy. Tracking the children from preschool ages to adolescence provides a rare opportunity to learn whether early brain overgrowth contributes to later problems in functional connectivity in the brain. The other study (Tal Kenet, Ph.D., Massachusetts General Hospital) will examine whether the abnormal connectivity patterns can explain the unusual sensory perceptions experienced by individuals with autism. By attempting to delineate both the nature and consequence of abnormal brain connectivity, these studies are designed to increase our understanding of brain functioning in autism so that interventions to enhance the development of normal brain circuitry can be developed.
For a complete listing of Basic and Clinical grant abstracts, click here.
“We are extremely pleased to announce these new set of pilot study and basic and clinical research grants,” said Dr. Dawson. “All of these grants were chosen for their potential impact on quality of life of individuals with autism and the development of new treatments.”
Year to date, Autism Speaks has awarded a total of more than $10.7 million in new science research grants, including grants announced in July that will investigate various aspects of genetics in preventing autism, interplay between genetics and environmental factors, the role of the immune system, and exploring the intellectual capability of individuals with ASD.
Pilot Study Grants
Autism Speaks will award $893,265 in new funding commitments for eight pilot study grants. These grants draw new investigators into the field of autism research and allow researchers to collect preliminary data to demonstrate the plausibility of an innovative area of exploration.
Several of the grants selected for funding directly address current issues of parent concern. As a large number of children with autism are transitioning into adolescence, their ability to navigate safely in our society without prejudice is of foremost concern for all. One pilot study (Elizabeth Kelley, Ph.D., Queen's Univ.) will address social difficulties in adolescents with Asperger's or high-functioning autism by identifying the behavioral factors that can lead to the “bullying” or victimization of these children by their peers. The study has the potential to identify better ways for parents and teachers to intervene in order to promote social inclusion.
Another pilot study (Avi Reichenberg, Ph.D., Institute of Psychiatry, King's College London) will examine a potential risk factor for autism, assisted reproductive treatment (such as in vitro fertilization), that has raised concern. Researchers will examine population-based data covering the past two decades to determine whether there is a link between the use of assisted reproductive treatment and risk for autism.
Sleep problems are another common concern voiced by parents. However, assessing such sleep problems is challenging. One group of researchers (Gregory Barnes, M.D. Ph.D., Vanderbilt Univ.) will examine whether epilepsy-associated patterns of brain activity during sleep can be linked to behavioral problems in children with autism while they are awake. Results from this study will help identify some of the causes of sleep disruption in autism and will allow clinicians to better plan treatments to help children sleep well at night and function better during the day.
Two researchers will conduct separate large-scale analyses of genetic risk factors. One study (Kathleen Millen, Ph.D., Univ. of Chicago) will explore a set of genes involved in the development of the cerebellum, a region of the brain that is often anatomically abnormal in people with autism. The researchers hope that focusing on genes involved in cerebellar development will provide clues to the genetic causes of autism. In another study (Maja Bucan, Ph.D., Univ. of Pennsylvania), researchers will use very new bioinformatics approaches to examine whether several autism susceptibility genes are involved in a molecular pathways. This work can help translate our knowledge about genes into an understanding of how those genes may interact and affect the biochemistry of the body. Both of these projects should help scientists better understand how multiple different genes converge on common biochemical pathways that lead to autism. Such studies are of great relevance to treatment because research in other disorders has shown us that targeting biochemical pathways, as opposed to the function of an individual gene, may help inform useful treatment strategies.
Two other projects will focus closely on the biology of a particular set of genes, called the neurexins and neuroligins. Mutations in these genes have been found some individuals with autism. The proteins made by these genes are thought to be involved in the function of synapses, the connections between neurons. One pilot study (Davide Comoletti, Ph.D., Univ. of California San Diego) will determine how these mutations affect the ability of the proteins to bind to each other. This knowledge may lead to an opportunity to correct the abnormal interaction. In the second study (Linda Restifo, M.D. Ph.D., Univ. of Arizona), researchers will develop a new automated method to study the functions of neuroligins and neurexins. They will use neurons engineered to make the mutated proteins and test them in a high-throughput screen of FDA-approved drugs. This will evaluate the ability of candidate drugs to reverse the effects of these autism-associated mutations. These neurons will also be tested for their sensitivity to thimerosal.
Finally, a new animal model will be created to focus on the properties of neurons expressing oxytocin and vasopressin, two neuropeptides involved in normal social behavior (Shlomo Wagner, Ph.D., Haifa University). The precise network of neurons that utilize these peptides is not known, which has greatly hindered progress in understanding their exact function. The researchers will now develop lines of genetically engineered mice that can be used to identify, observe, and manipulate these neurons. This work may provide a foundation for parallel research into if and how these networks are disturbed in people with autism, and whether modulation of the peptides may serve as a viable treatment option.
For a complete listing of Pilot grant abstracts, click here.
Basic and Clinical Grants
Autism Speaks will award $1,523,172 in new funding commitments for five basic and clinical research studies. Topics selected for funding include potential prenatal factors that confer a risk of autism, the identification of subtypes of sleep and behavioral problems in children with autism, and how neural connectivity is affected in the brains of individuals with autism.
Two studies will examine prenatal environmental factors that may cause neurodevelopmental problems in the fetus, contributing to a higher risk of autism. One study (Richard Ebstein, Ph.D., Hebrew Univ.) will take an epidemiological approach to examining the role of drugs that are commonly administered to pregnant women to either prevent or induce labor. The other study (Theo Palmer, Ph.D., Stanford Univ.) will investigate how activation of the maternal immune system during pregnancy affects fetal development, focusing on the effects of maternal infections on placental functioning. If infections perturb the supply of blood and oxygen to the developing fetus, fetal brain development could be affected. These studies have the potential to suggest new preventative measures that can be taken during pregnancy.
Another study (Susan Mayes, Ph.D., Penn State College of Medicine) will conduct a large-scale analysis of the associations between sleep problems and behavior in children with autism. Determining whether any particular sleep disturbances are correlated with specific learning, mood, or behavioral problems will not only be invaluable in developing strategies to improve behavior in children with autism, it will offer an opportunity to immediately have a positive impact on the quality of life for families.
Finally, an emerging theory regarding the biological basis of autism is that the disorder results from changes in neural connectivity in the developing brain. Using recently developed non-invasive techniques to measure brain activity and the communication between different brain regions, two projects will study neural connectivity. In a very unusual opportunity to examine data collected on the same subjects over the time span of a decade, one imaging study (Natalia Kleinhans, Ph.D., Univ. of Washington) will use a longitudinal approach to draw a relationship between altered functional brain connectivity in adolescents at age 15 and atypical head growth that occurred much earlier during their infancy. Tracking the children from preschool ages to adolescence provides a rare opportunity to learn whether early brain overgrowth contributes to later problems in functional connectivity in the brain. The other study (Tal Kenet, Ph.D., Massachusetts General Hospital) will examine whether the abnormal connectivity patterns can explain the unusual sensory perceptions experienced by individuals with autism. By attempting to delineate both the nature and consequence of abnormal brain connectivity, these studies are designed to increase our understanding of brain functioning in autism so that interventions to enhance the development of normal brain circuitry can be developed.
For a complete listing of Basic and Clinical grant abstracts, click here.
“We are extremely pleased to announce these new set of pilot study and basic and clinical research grants,” said Dr. Dawson. “All of these grants were chosen for their potential impact on quality of life of individuals with autism and the development of new treatments.”
Year to date, Autism Speaks has awarded a total of more than $10.7 million in new science research grants, including grants announced in July that will investigate various aspects of genetics in preventing autism, interplay between genetics and environmental factors, the role of the immune system, and exploring the intellectual capability of individuals with ASD.
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