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Basis of developmental disabilities focus of $11.3 million in grants

Research to examine genetic, environmental factors linked to such disabilities and how to improve lives of those affected

by Jim DrydenOctober 2, 2020

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Researchers at Washington University School of Medicine in St. Louis have received a pair of grants totaling $11.3 million to study genetic and environmental factors that contribute to developmental disabilities and to find new ways to improve the lives of children and adults affected by such disabilities.

The grants — a five-year award from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, and a four-year grant from the National Center for Advancing Translational Sciences, both of the National Institutes of Health (NIH) — renew funding for the university’s Intellectual and Developmental Disabilities Research Center (IDDRC).

The center opened in 2010 and is one of 13 such centers in the United States. Work at the IDDRC focuses on clinical and translational research, emphasizing four key areas of impact: prevention of premature birth and its consequences; identification of clusters of symptoms in infants that put them at risk for developmental problems; detailed characterizations of the developing human brain; and use of genomics to identify treatment targets for specific disorders in individual children.

The center’s directors are John N. Constantino, MD, and Christina A. Gurnett, MD, PhD. Constantino is the Blanche F. Ittleson Professor of Psychiatry and Pediatrics. He directs the William Greenleaf Eliot Division of Child and Adolescent Psychiatry and is psychiatrist-in-chief at St. Louis Children’s Hospital. Gurnett is the A. Ernest and Jane G. Stein Professor of Developmental Neurology. She directs the Division of Pediatric and Developmental Neurology and serves as neurologist-in-chief at St. Louis Children’s Hospital.

In addition, Joshua B. Rubin, MD, PhD, a professor of pediatrics, of neurology and of neuroscience, and Cynthia Rogers, MD, an associate professor of child psychiatry, serve as the center’s associate directors. Alan L. Schwartz PhD, MD, a professor of pediatrics and of developmental biology, is the center’s senior advisory liaison to several committees that advise the IDDRC. Others involved include senior scientists in genetics, neuroscience, psychological & brain sciences, radiology and other disciplines critical to advancing the understanding of developmental disabilities.

“In the next phase of the IDDRC at Washington University, our strategy is to accelerate our work in understanding the ways in which individually rare genetic variants interfere with brain and behavioral development,” Constantino said. “Two new features of the program are a planned national registry for patients with abnormalities in brain genes, and a dedicated unit for studying patient-derived neuronal cell lines that will be used to model rare conditions in individual patients, with a goal of deriving new treatment targets.”

A central project — to be led by Jeffrey R. Milbrandt, MD, PhD, the James S. McDonnell Professor and head of the Department of Genetics, and Robi Mitra, PhD, the Alvin Goldfarb Professor of Computational Biology and a professor of genetics — will use the cell-line models to identify mechanisms that cause problems in numerous genetic conditions associated with developmental disabilities. Their goal is to identify targets for prevention and treatment that might benefit large numbers of individuals at risk, not just those who have rare genetic conditions.

As the center takes advantage of sophisticated technologies to model and understand how brain cells function in individual patients, it is formulating ways to translate that understanding into interventions that offset genetic and environmental influences linked to the causes and severity of intellectual and developmental disabilities.

“Now that the genes responsible for intellectual and developmental disabilities are known for at least some children, the IDDRC is pivoting to support the implementation of clinical trials for rare diseases,” said Gurnett. “Our patients and their families need us to be ready to do this critical work.”

Gurnett and Constantino said that the IDDRC works closely with similar centers around the United States. The goal is for all 14 centers to harness their individual strengths and share resources with those at the other centers to quickly transfer new discoveries into interventions that may improve the lives of individuals with developmental disabilities.

Washington University School of Medicine’s 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Jim retired from WashU Medicine Marketing & Communications in 2023. While at WashU Medicine, Jim covered psychiatry and neuroscience, pain and opioid research, orthopedics, diabetes, obesity, nutrition and aging. He formerly worked at KWMU (now St. Louis Public Radio) as a reporter and anchor, and his stories from the Midwest also were broadcast on NPR. Jim hosted the School of Medicine's Show Me the Science podcast, which highlights the outstanding research, education and clinical care underway at the School of Medicine. He has a bachelor's degree in English literature from the University of Missouri-St. Louis.