$8.7 million grant awarded to researchers to study cause of intellectual disability

Drs. Sweeney and Huber
(l–r) John Sweeney, Ph.D., Professor of Psychiatry and Pediatrics, and Kimberly Huber, Ph.D., Professor of Neuroscience, examine data at the UT Southwestern Center for Autism and Developmental Disabilities. They will lead research into Fragile X Syndrome funded by the National Institute of Health.

By Gregg Shields

Researchers at UT Southwestern Medical Center received an $8.7 million grant from the National Institutes of Health to study Fragile X syndrome, the most common inherited cause of intellectual disability in boys. The genetic condition causes a range of developmental problems, including learning disabilities and cognitive impairment, with males typically more severely affected than females.

Fragile X syndrome affects a single gene, FMR1, that is located on the X chromosome. The FMR1 gene provides instruction for making a protein called fragile X mental retardation 1 protein. The syndrome gets its name from the fact that under a microscope, the area around the FMR1 gene looks narrower than normal, or “fragile.” The inherited condition causes a distinct physical appearance, including an elongated face with protruding ears, hyper-flexible joints, and mental deficits ranging from mood disorders to features of autism.

Kimberly Huber, Ph.D., Professor of Neuroscience, and John Sweeney, Ph.D., Professor of Psychiatry and Pediatrics, and holder of the Townsend Distinguished Chair in Research on Autism Spectrum Disorders, will lead the research.

Many people with Fragile X syndrome are sensitive to sensory stimuli, especially noise. The new funding will enable novel translational research, as UT Southwestern investigators strive to determine the causes of this heightened sensitivity to sound.

Dr. Huber and Jay Gibson, Ph.D., Associate Professor of Neuroscience, will investigate brain circuitry in mice with Fragile X syndrome. Their aim is to determine the neurobiological causes of brain dysfunction in the syndrome with the hope of uncovering targeted therapies that will correct the deficits.

Dr. Sweeney will focus his investigation on heightened excitability in the cortex of the brain through studies of electroencephalography (EEG) and brain chemistry. His research will screen for effects of new therapeutics on brain function that may aid in the identification of responsive patients in clinical trials with Fragile X syndrome and autism spectrum disorders.

UT Southwestern researchers have already made great progress in understanding Fragile X syndrome. For more than a decade, Drs. Huber and Gibson, an immensely successful husband-wife team, have studied the FMR1 mutation in mouse models. Their research led to an understanding of how brain circuitry changes in these models.

The five-year NIH grant also will fund collaborators working at the University of California, Riverside. This collaboration will allow a direct comparison of brain circuit dysfunction and therapeutic efficacy in both mice and patients with Fragile X syndrome. 

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Dr. Sweeney holds the Townsend Distinguished Chair in Research on Autism Spectrum Disorders.