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Aiming at MAR autism
SACRAMENTO, Calif.—Prof. Judy A. Van de Water of the University of California, Davis (UC Davis) has been awarded an Individual Biomedical Research Award from the Hartwell Foundation for her recent research in autism. The award consists of $100,000 direct costs each year for three years.
Van de Water’s research focuses on how certain antibodies found in pregnant women can affect their gestating children. Last year, she detailed how antibodies found in the bloodstream in some pregnant women target proteins that play a pivotal role in fetal brain development, a discovery that provides the first definitive cause for a subset of cases with non-genetic causes of autism. Van de Water refers to the 23 percent of autism cases associated with the mother’s autoantibodies as maternal autoantibody-related (MAR) autism.
The study, “Autism-specific maternal autoantibodies recognize critical proteins in developing brain,” was published July 9, 2013 in the Nature journal Translational Psychiatry. It found that mothers of autistic children were 21 times more likely than mothers of children without autism to have specific MAR antibodies in their systems that reacted with fetal brain proteins. Maternal antibodies cross the placenta during pregnancy and are detectable in a fetus as early as 13 weeks, while by 30 weeks, maternal antibody levels are roughly half that of the mother. By the time the child is born, it has a greater concentration than its mother of the maternal antibodies, which stay in the baby’s bloodstream until it is approximately six months of age, at which point the baby’s immune system takes over.
In order to identify the antigens targeted by the maternal antibodies, Van de Water and colleagues used blood samples from 246 mothers of autistic children and from a control group of 149 mothers of children without autism. Their work showed seven antigens that were markedly more reactive to the blood of the autistic children’s mothers than that of those in the control group: lactate dehydrogenase A and B, cypin (guanine deaminase), stress-induced phosphoprotein 1, collapsing response mediator proteins 1 and 2 and Y-box binding protein. All seven antigens can be found throughout the body, but are expressed at high levels in the fetal brain, having known roles in neurodevelopment. In addition, it was found that women with antibodies that reacted to any of the seven antigens—singly or in combination—were more than three times as likely to have an autistic child.
“The availability of a therapy to prevent MAR autism has the potential to eliminate nearly one in four cases of autism among U.S. children. If successful, such a therapy will improve the quality of life for children who would have been affected, as well as their families, while also reducing the estimated $29 billion per year in societal cost currently incurred through autism therapies,” Van de Water said.
She is seeking a method for targeting the autoantibodies to fetal brain proteins with antibody-blocking peptides—namely, smaller, synthetic segments of specific fetal brain protein. Her future research, supported by the Hartwell Foundation award, would evaluate the peptides’ effectiveness in blocking fetal exposure to the maternal antibodies in a mouse model of MAR autism while maintaining normal behavior in offspring. If these autoantibodies could be detected early in pregnant women, it could allow for early medical interventions to limit the exposure of the fetus to the autoantibodies and, in turn, limit the risk of the child developing an autism spectrum disorder.
According to the U.S. Centers for Disease Control and Prevention, roughly one in 68 children in America register somewhere on the autism spectrum, “a 10-fold increase in prevalence in 40 years,” as noted on the Autism Speaks website.” Given that “the most obvious signs of autism and symptoms of autism tend to emerge between 2 and 3 years of age,” the website notes, a method of identifying mothers at risk of having children with autism due to their antibodies could allow for much earlier intervention.