This proposal has three linked and interacting projects designed to (1) develop new therapy for children with autism, (2) develop means of validating and monitoring responses to therapy assessed through clinical changes in the children and the amount of certain lipid biomarkers that they excrete in their urine, and (3) develop means for selecting children with autism likely to respond to this therapy based upon the children's genotypes, that is, the pattern of variants of certain key genes that the children have.
The rationale is that growing evidence supports oxidative stress as a mechanism that contributes to autism. A key omega-3 fatty acid called docosahexaenoic acid (DHA) is a normal substance that is present in large amounts in the brain and that has properties that oppose oxidative stress. Therapeutic trials of agents containing DHA appear promising in autism. We were first to find that urinary excretion of a lipid biomarker of oxidative stress is increased in autism. In a preliminary study, we found that the amount of this biomarker excreted in children with autism correlated with a certain genotype in the children.
We propose to carry out a rigorous therapeutic trial to assess the effect of DHA vs. placebo treatment on the global severity, behavioral symptoms, and functional ability of child and adolescent autistic disorder, in a 12-week double blind placebo-controlled parallel study (Project 1). We propose to measure changes in urinary excretion of this biomarker, isoprostane, during DHA therapy in the children with autism and develop new urinary biomarkers that may be even more informative (Project 2). We also propose to determine genotypes of the children undergoing DHA therapy since we found one gene variant, GSTM1*0, that correlated with the amount of isoprostane that children with autism excreted in their urine in a preliminary study (Project 3). We will test whether this gene variant and new gene variants that we will study will correlate also with response to DHA treatment (Project 3). We hope that this will allow us to predict which children with autism will respond to DHA therapy. This may also give us insight into whether some children with autism have a gene variant that interferes with DHA metabolism.
This will help all children with autism by developing a new method of therapy, by developing a method to monitor the success of the therapy and show that it is working and by developing a method to determine which children with autism will respond best to the therapy.
The clinical benefits will be assessed for global severity of autism, and for behavioral and functional aspects of autism. The therapy is safe and has no known risks.
What is the projected time to achieve a consumer-related outcome? The study is a direct therapeutic trial. If the trial is successful, this therapy will be available to consumers by the end of the three-year project.
The likely contributions of this study are (1) development of new therapy for autism, (2) development of a way to determine if the therapy is working in a child with autism and how well it is working, and (3) to develop a way of determining which children will respond best to the therapy.