SALT LAKE CITY – A multidisciplinary team of University of Utah investigators has received a grant for innovative research that will shed new light on the genes that cause Down syndrome (DS), as well as the defects of brain development and function that lead to intellectual disability. The $2.96 million grant, co-funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH), will support cross-disciplinary research that studies not only genes and brain structure, but also the circuitry and chemical signals within the brain that lead to the development of DS.

“We’ll be taking a revolutionary first look at how brain circuits are related to behavior, intelligence, and brain function,” said University of Utah USTAR Professor Julie R. Korenberg, Ph.D., M.D. “The team’s approach to the study of Down syndrome is unprecedented and integrates genetics, neuroimaging and cognitive testing into the research. Winning this highly competitive grant speaks well to the university and to the support we’ve received from the entire Down syndrome community in Utah.”

The team Korenberg has brought together—the DS Therapeutic Consortium—is a group of internationally recognized investigators at the University of Utah who represent more than 10 highly interactive departments with a strong commitment to DS research. Local families, coordinated through the Utah Down Syndrome Foundation (UDSF), will participate in the study.

“Our state has an amazing network of support, which includes families, community members and professionals,” commented Ann Marie Christensen, UDSF board president. “The UDSF is happy to strengthen these bonds of support by working with such a wonderful group of medical professionals for the potential benefit of all individuals with Down syndrome.”

DS affects more than 400,000 individuals in the United States and is the most common genetic cause of cognitive disability and Alzheimer’s disease. In addition to defects in memory, language, and brain anatomy, DS is also associated with physical changes, congenital heart disease, and abnormal intestinal development. Individuals with DS are born with an extra copy of all or most of the genes on chromosome 21. While most genetic diseases are caused by mutations on a single gene, the characteristic features and developmental problems of DS are a complex function of more than 220 genes on chromosome 21.

There have been significant advances in the understanding of DS in the past 10 years, including research on treatments that boost the growth of brain cells and improve memory. However, most of these studies were performed in mice with an equivalent of DS. Korenberg and her colleagues will be studying DS in humans, including a unique group of individuals with DS caused by duplication of only part of chromosome 21, a rare condition referred to as partial trisomy 21. Korenberg, a professor of pediatrics at the U of U medical school, has amassed the world’s largest cohort, or patient group, with this characteristic. People with partial trisomy 21 provide a unique opportunity to link specific genes with defects in brain development and function.

Even though a complete list of chromosome 21 genes has been identified, researchers still don’t know which of those genes is responsible for the mental disability associated with DS, Korenberg said. “Now, powerful advances in medical genetics and human brain imaging have given us new techniques to link genes to the structural abnormalities and changes in brain circuitry that occur in people with DS. The ultimate goal is to develop novel treatments for DS and other intellectual disabilities.

“The University of Utah has fantastic talent and resources in toxicology, imaging, pediatrics, mouse behavior, data management, and more. Around NIH circles, we heard the term ‘dream team’ used, and I think that’s accurate,” Korenberg said.

The team assembled on this new grant includes co-principal investigator and imaging expert Guido Gerig, Ph.D., a USTAR professor at the University of Utah’s Scientific Computing and Imaging Institute. Other key team members include: E.K. Jeong, Ph.D., associate professor of radiology; Jeffrey L. Anderson, M.D., professor of cardiology; John C. Carey, M.D., professor of pediatrics; and Nicola Longo, M.D., Ph.D., professor of pediatrics. University of Arizona psychology researchers Lynn Nadel and Jamie Edgin are also participating.