Researchers at the University of South Carolina are leading the country to improve the health of millions of people with fragile X disorders — some of the most common but least-known neurological disorders.
USC recently received a National Institutes of Health Center of Excellence grant that will enable researchers to show how the fragile X premutation affects children and adults. This includes the first study ever to track development of children with the fragile X premutation across the first five years of life, as well as a study of how conditions affect the brain health of adult women.
“This Center of Excellence grant brings together scientists, clinicians and community partners committed to improving the quality of life for people affected by fragile X,” Jane Roberts, executive director of the Carolina Autism and Neurodevelopment Research Center, said. “Our work will improve understanding of how fragile X-associated conditions develop and change over time, leading to better diagnosis and treatment for individuals across the lifespan. We are proud to be a national leader in this effort.”
The fragile X research is part of USC’s expansive research focus on brain health. Over the past decade, USC is the top university recipient of NIH grants for studying fragile X conditions in humans, with awards totaling nearly $27 million since 2015.
“I’m proud, but not surprised, that this outstanding research team has been awarded a prestigious NIH Fragile X Center of Excellence award,” said Julius Fridriksson, USC Vice President for Research. “Having this center in South Carolina will enable the researchers to generate new discoveries to help people living with this disorder and provide education and support for individuals and families who choose to get involved with the center’s studies — it’s a win-win.”
Fragile X results from a mutation of the FMR1 gene on the X chromosome. As one of the most common inherited neurodevelopmental disorders, fragile X is a leading genetic cause of autism, but it also is linked to a variety of other health conditions.
USC scientists have worked with fragile X patients and their families for almost 20 years to better understand and improve symptoms. The new Center of Excellence grant allows them to expand research about health challenges related to the FMR1 premutation, which affects up to 1 in 150 women and 1 in 268 men and results in unique health challenges.
Roberts, a Carolina Distinguished Professor in the McCausland College of Arts and Sciences, said the approach of this grant allows scientists to look for unique solutions to enhance life for people with fragile X and similar and related conditions, including autism.
“By taking a lifespan approach — studying infants through adults — we can uncover how age, biological sex and life experiences influence the development of fragile X conditions,” Roberts said. “The overarching goal is to identify signs and biological pathways that could lead to earlier detection and better treatment options. Ultimately, this supports thousands of patients and their families.”
One project supported by the grant will expand research about infants and children with Fragile X-associated Neuropsychiatric Disorders (FXAND), who may have autism, anxiety, learning difficulties and social differences.
Roberts has worked with Abigail Hogan and Jessica Klusek, professors in USC’s Arnold School of Public Health, to study the development of infants from 6 months to 2 years. The new grant will allow them to check in with those children until age 5. They also will recruit new children into the study from a wider range of racial and income backgrounds.
Their initial research with infants and children already made one breakthrough: the USC researchers found that infants with the FMR1 premutation were more likely to show signs of autism and anxiety, Hogan said. Previously, clinicians and scientists had assumed the premutation did not affect young children.
By expanding the study to include more children and follow them through age five, the researchers will learn more ways to help children at risk of these conditions, Hogan said.
“This study will allow us to better understand how, when, and why anxiety and autistic features develop in young children with the FMR1 premutation,” Hogan said. “This knowledge will lead to earlier identification and diagnosis, which in turn facilitates early interventions that can help children learn and grow, and can help ensure the best possible outcomes for children and their families.”
Meanwhile, Klusek will lead a study of Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) in women ages 35 to 80. FXTAS is a neurodegenerative disorder in adults resulting in cognitive decline, tremors and muscle control problems. Although FXTAS affects both males and females with the FMR1 premutation, women have been underrepresented in prior research on FXTAS. Addressing this gap, Klusek’s research will help reveal when and why FXTAS symptoms begin in women, and how clinical, genetic and environmental factors may play a role.
“For years, women have been left out of the FXTAS picture, and that’s meant a lot of uncertainty for families,” Klusek says. “Our goal is to change that by giving women with the FMR1 premutation clearer information about their health risks and how those risks may evolve over time. This will bring us closer to early and accurate diagnoses, better monitoring, and eventually better treatments for women with FXTAS.”
The projects are supported by a $6.3 million NIH Fragile X Center of Excellence award, a highly competitive award that establishes national research hubs to transform scientific understanding and clinical care.
In addition to Roberts, Hogan and Klusek, USC faculty Jeffrey Twiss, Caitlin Hudac, Amanda Fairchild, Sarfaraz Serang (McCausland College of Arts and Sciences), Meisam Arjmandi and Xiaoming Li (Arnold School of Public Health) and Marlene Wilson (School of Medicine, Columbia) will work with the Center of Excellence. Other collaborators include scientists at Rush University, the Research Foundation for Mental Hygiene, University of Wisconsin-Madison, Medical University of South Carolina, and the Donovan Angel Foundation.