RIVERSIDE, Calif. -- A new research project at the University of California, Riverside, has received funding to investigate whether a novel protein-based therapy can correct abnormal brain activity associated with Fragile X syndrome.
Affecting about 100,000 Americans, Fragile X syndrome is caused by changes affecting the FMR1 gene and the production of FMRP, a protein important to normal brain development and function. It can cause intellectual disability, learning and memory difficulties, social and behavioral challenges, and unusual sensitivity to sensory stimuli. Fragile X is also an important genetic cause of autism spectrum disorder.
The one-year, $100,000 grant from the FRAXA Research Foundation will support research in the laboratory of Dr. Devin Binder , a professor of biomedical sciences in the School of Medicine . The project will use a mouse model of Fragile X syndrome to test several protein candidates developed by the biotechnology company Bowen’s FX Therapeutics . The proteins are designed to replace the function of a protein that is missing or impaired in people with the disorder.
For Binder, the project brings together years of research into the abnormal brain activity associated with Fragile X and recent advances in protein engineering that could make it possible to deliver a therapeutic protein to the brain.
“What our collaborators are doing is possible now in a way that I never thought was possible when I first entered this field,” Binder said. “They can engineer a protein and get it into the brain and cells. A few years ago, that would have seemed like science fiction.”
Scientists have a well-established animal model to study Fragile X: the Fragile X knockout mouse. These mice exhibit several brain abnormalities that resemble those observed in people with the condition, including changes in how the brain processes sensory information and coordinates neural activity.
Binder’s laboratory has studied Fragile X and epilepsy for years, focusing on measuring brain activity in animals. One of the lab’s principal tools is electroencephalography, or EEG.
“We’re looking at the whole animal as it’s actually behaving and processing stimuli,” Binder said. “Our goal is to obtain very high-quality brain recordings from the mice.”
His lab has previously identified specific EEG abnormalities in Fragile X mice. Those measurements provide a baseline for testing whether the new protein treatments can restore normal brain function.
Binder explained that one of the major challenges in treating neurological disorders is getting a therapeutic molecule across the blood-brain barrier, which limits the passage of many substances from the bloodstream into the brain.
According to Binder, Bowen’s FX Therapeutics has used protein engineering to develop versions of the Fragile X-related protein that can be administered systemically and cross the blood-brain barrier. Binder’s lab will test whether the treatment changes brain physiology in the Fragile X animal model.
Carrie Jonak , a research associate in Binder’s laboratory, generated the preliminary data that helped support the grant application and will carry out much of the research.
Binder and Jonak have a straightforward measure of success.
“If the Fragile X mice after treatment begin to resemble the normal mice, if their physiology is essentially normalized, that would be a very significant result,” Binder said.
The pilot study will not directly determine whether the mice become better at learning or remembering. But if the treatment corrects abnormalities in brain activity, Binder said, his team would predict some associated cognitive and behavioral problems could also improve.
“I see this project as an example of how foundation funding can bring together academic neuroscience and biotechnology,” he said. “Bowen’s FX Therapeutics provides access to a promising therapeutic technology, while my laboratory brings expertise in measuring brain activity in living animals. As academics, we otherwise wouldn’t necessarily have access to these kinds of therapeutics.”
The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment is more than 27,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual impact of more than $2.7 billion on the U.S. economy. To learn more, visit www.ucr.edu .