In March of 2008, Autism Speaks released a Request For Applications that solicited proposals for projects that focused on studying environmental contributions to autism, with a special emphasis on environmental factors and their interaction with genetic risk factors. In response, 60 applications were received. These included pilot applications to test new hypotheses and gather preliminary data, as well as augmentation applications that would expand current large scale studies to include a new focus on the role of the environment in autism. Additional applications were sought for workshop ideas that could bring together researchers from different areas of expertise to tackle challenges in specific areas of environmental exposure and autism.
In response, Autism Speaks funded 12 applications, for a total of $3.6 million dollars over the next three years. The applications ranged in approach and scope, but included areas of toxicology, immunology, epigenetics, and animal models. Dr. Yong-hui Jiang at Baylor College of Medicine will be studying how folic acid supplementation, which has increased significantly over the past decades, affects epigenetic modulation of SHANK3 protein expression. This is of importance since mutations of the SHANK3 gene have been reported to be altered in individuals with autism. Epigenetics (alterations in gene function without changes in DNA structure) has received recent attention in autism spectrum disorders and may be influenced by environmental factors. Dr. Robert Plomin at the Institute of Psychiatry in London will be using an existing twin registry to examine differences in epigenetic markers between identical twins who do not share a diagnosis of autism. Dr. Emile Rissman from the University of Virginia will be targeting a widely used chemical called Bisphenol A, an ingredients in some plastics, to determine if exposure induces epigenetic modifications.
Another environmental factor that will be investigated is Vitamin D, Dr. Bruce Hammock at the University of California at Davis will be utilizing the CHARGE study, which has collected blood from over 500 families affected by autism, to examine whether and why children with autism show differences in Vitamin D levels. Recently, the lack of Vitamin D in mothers and children has been reported as a potential health concern that could influence brain development and function.
The role of the immune system was another predominant topic of environmental sciences applications. Altered immune function could be a target of environmental toxicant exposure. The immune status of the fetus during development constitutes an important environmental factor in brain function. Dr. Nicholas Ponzio from the University of Medicine and Dentistry of New Jersey will be examining how T cells and cytokines function in the brain and the placenta, as well as how they affect the developing fetus. Also, Dr. Judy Van de Water at University of California at Davis is partnering with Vanderbilt University researchers to study how changes in the expression of the MET gene, shown to be associated with autism, regulate maternal autoantibody production. More importantly, this study will also examine how environmental toxicant exposure, including ethylmercury (the major component of thimerosal) as well as a common environmental toxicant BDE-47, influences cytokine production. While the Van de Water study will examine how autoantibodies are produced, the effects on brain development of maternal autoantibodies in the prenatal environment will be studied by Dr. Betty Diamond at the Feinstein Institute.
Three projects will focus on the potential role of vaccines, specifically the role of ethylmercury or other vaccine components. These include a project by Dr. Flavio Keller at the University Bio-Medica in Rome, who will study the behavioral and pathological effects of ethyl and methyl mercury on a strain of mice that possess a certain mutation in order to examine gene and environment interactions. Dr. Mark Noble from the University of Rochester will use a genetically modified cell line to study the effects of ethylmercury and aluminum hydroxide on oxidative potential. Finally, Dr. David Baskin from Methodist Hospital in Houston, will study cell proliferation in response to thimerosal exposure.
Autism Speaks is committed to funding innovative projects on potential environmental contributions to autism spectrum disorders. Thinking broadly about the role of particular exposures and how they interact with genetic risk factors are priorities of Autism Speaks research.