Autism Spectrum Disorder ASD) is a complex developmental disability characterized by problems with social interaction and communication. Symptoms start before age three and cause delays or impairments in different skills that develop from infancy to adulthood. ASD affects 1 in every 110 children in the U.S.
In the past years, studies have suggested a maternal contribution to some cases of ASD. In a very large study we have shown that mother of an ASD child are 4 times more likely have antibodies that bind brain-tissue, and these women with brain-reactive antibodies exhibit other features of autoimmunity. Previous studies showed that when serum or IgG that bound to brain tissue from a mother of an ASD child were given to pregnant mice or pregnant monkeys, they caused behavior abnormalities in the offspring.
Based on this evidence, we hypothesized that in some cases of ASD, antibodies to brain tissue transfer from the mother through the placenta to the fetus. These antibodies do not injure the mother because she has an intact barrier between the blood and the brain that prevents these antibodies from targeting brain tissue. In the fetus, this barrier is not fully developed; antibodies can cross the placenta, enter the fetal circulation, bind to the developing brain and potentially cause the symptoms of ASD.
We now have generated a panel of monoclonal anti-brain antibodies from mothers of an ASD child. We propose to identify the molecules in the brain bound by those antibodies and to determine which antibodies affect the brain in a way that results in ASD. Studies with one such monoclonal antibody proved the feasibility of this approach. The goal of this program is to develop small molecules that are bound by the antibodies and neutralize their toxicity to the fetal brain. This will offer the possibility of prevention of a proportion of ASD.