Autism Speaks has announced more than $4.5 million in grant awards for basic and clinical research dedicated to autism. The funded projects take a variety of approaches towards revealing the underlying biology and causes of autism.
"We are pleased to be funding such innovative and important work. The studies will range from applied research on new methods for clinical assessment to basic research on molecular genetics," noted Geri Dawson, Chief Science Officer of Autism Speaks.
Two types of grants were awarded: two-year Pilot grants that explore newer, particularly innovative lines of research, and three-year Basic and Clinical grants that build on more established research. Competition for these awards was intense, with only slightly more than 10% of the grants submitted ultimately receiving funding. These highly select projects reflect the growing sophistication of autism science, and tackle important questions that can advance our understanding of autism.
Studies will focus on the interaction between genes and environment in the etiology of autism
One project investigates the role of mitochondria dysfunction in autism (Giulivi), a topic that has received much attention recently. Mitochondria are the energy machines of cells, and some studies have suggested that there are changes in energy metabolism in autism. This project will study the role of the PTEN gene, which has been implicated in autism and is potentially involved in mitochondrial function in mice genetically engineered to lack this gene.
Attempting to unravel how genes and environmental factors may interact to produce risk for autism, two grants will explore the impact of prenatal exposure to specific environmental factors in mice with specific genetic abnormalities. One project will study the effects of organophosphate exposure in combination with low levels of the reelin gene, which is important for brain development (Carpenter). Another will examine the effects of the maternal immune response, which can be thought of as an environmental factor for the developing fetus, in combination with DISC1 gene mutations, which interfere with brain development (Pletnikov). By identifying the complex molecular mechanisms behind gene-environment interactions, this research can lead to a better understanding of the risk factors for autism and eventually lead to novel treatments and prevention strategies.
Because the prenatal period is a crucial time for brain development, the uterus itself may be a source of environmental factors relevant to autism. As mentioned above, this may include immune system molecules made by the mother. For example, injecting a molecule called IL-2 into pregnant mice leads to abnormal offspring, and one project will focus on uncovering exactly how IL-2 interferes with prenatal development (Ponzio). A second project will take a much broader approach to this topic and study how immune system molecules (i.e., cytokines and autoantibodies) present during pregnancy may influence risk for autism (Croen). The large study cohort will include mothers of children with autism as well as mothers of children with other developmental delays and mothers of children with typical development . This work will help specify how the network of immune system molecules called into action during pregnancy may be relevant to the development of autism, leading to strategies for intervention.
Most genetics research has focused on finding genes that lead to an increased risk of developing autism. One project now takes the unique tack of looking for genes that protect an individual from developing autism (Persico). Because autism runs in families, the researchers hypothesize that unaffected siblings could also have the autism susceptibility genes, but that they might also have protective genes that somehow prevent the susceptibility factors from taking hold. Identifying protective gene variants is a novel approach toward developing ways to offset the impact of autism susceptibility.
Projects offer promise of understanding the biological basis of autism, new methods for testing language comprehension
To delve into the neurochemistry of autism, two projects are geared toward understanding the role of a neurotransmitter called serotonin. Serotonin is involved in sending signals between neurons in the brain, and atypical serotonin function has been implicated in autism. One project will study the role of the serotonin transporter protein, which controls serotonin levels in the brain. A rare mutation in the gene that makes this protein has been found in some cases of autism, and so researchers will engineer mice to carry this mutation to determine whether it directly leads to autistic-like behaviors (Veenstra-VanderWeele). A second study will investigate the links between serotonin function, brain activity, and its relation to social impairment in autism in humans (Monk). This will help research connect the dots between genes, brain and behavior in autism.
Two projects will explore the capabilities of people with autism. Because of their difficulties communicating, nonverbal individuals with autism are often assumed to be mentally-impaired. To better assess their communication skills, one study will test language comprehension in nonverbal individuals with autism by tracking their eye movements (Tager-Flusberg). This technique has been used with preverbal infants, and the researchers expect that those with autism will show greater understanding when it is measured using eye movements than with standard tests. A second project will focus on the enhanced visual perception of people with autism in an effort to identify the brain regions involved (Mottron). Together this kind of information can help develop appropriate treatment and learning strategies.