Title of Research Grant

Oxidative Stress and Down syndrome: Development of urinary biomarkers assays to monitor individuals with Down syndrome under treatment.


Adviye A. Tolun, MS, PhD, Dora Il’yasova, PhD, Sarah P. Young, PhD, FACMG, David S. Millington, PhD

Pediatrics - Medical Genetics
Department of Pediatrics
Biochemical Genetics Laboratory
Duke University

Lay Summary of Research

Down syndrome (DS) is a complex disorder with many symptoms that are distressing to individuals and their families. There is evidence indicating that at least some of these adverse clinical symptoms are caused by overproduction of chemicals called reactive oxygen species (ROS) that cause oxidative damage to cells and compromise their normal function. Therapy aimed at reducing the effects of these oxidative species might improve the clinical status of individuals with DS and improve their quality of life. Preliminary efforts have already been made to assess the clinical impact of antioxidant therapy on DS, but the results have been inconclusive due to poor design. We believe that better antioxidant trials with focus, on using the best antioxidants, at the right dose, for optimal duration, on the right patient group, will prove to be effective. Efforts to improve oxidative status must be coupled with measurable changes in compounds that reflect reduced oxidation of cells in the body. These compounds are referred to as biomarkers of oxidative stress. Although these biomarkers are difficult to measure, our laboratory has used state of the art technology to develop methods for this purpose. Our aim is to measure several of these biomarkers in the urine of individuals with DS and compare them with normal individuals. If, as expected, any or all of these biomarkers prove to be present at consistently higher concentration in individuals with DS, then we will have a valuable method to assess the effectiveness of therapies in future clinical studies.