UC Riverside tests protein therapy for Fragile X syndrome in new $100K study

At UC Riverside's School of Medicine, a research team has begun work on a question that seemed impossible just a few years ago: Can an engineered protein, delivered across the blood-brain barrier, restore normal brain function in people with Fragile X syndrome? The project, funded by a $100,000 grant from the FRAXA Research Foundation, will take one year to answer it—at least in mice.

Fragile X syndrome affects roughly 100,000 Americans. It stems from mutations in the FMR1 gene, which disrupts production of FMRP, a protein essential to how the brain develops and operates. The result is intellectual disability, difficulties with learning and memory, social and behavioral struggles, and heightened sensitivity to sensory input. The disorder is also a significant genetic driver of autism spectrum disorder. For decades, there has been no targeted treatment.

Dr. Devin Binder, a biomedical sciences professor, leads the research. His laboratory has spent years measuring abnormal electrical activity in the brains of Fragile X mice using electroencephalography, or EEG—essentially recording what happens inside an animal's brain while it behaves and responds to stimuli. Those recordings revealed specific patterns of dysfunction that serve as a measurable target. The question now is whether a new class of therapeutics can fix them.

The proteins being tested come from Bowen's FX Therapeutics, a biotechnology company that has engineered versions of the missing Fragile X protein to do something that was once considered science fiction: cross the blood-brain barrier. This barrier is one of medicine's great obstacles. It protects the brain but also blocks most therapeutic molecules from entering the bloodstream and reaching neural tissue. Bowen's team has designed proteins that can slip through. Binder's lab will administer these candidates to Fragile X mice and measure whether the treatment changes their brain physiology back toward normal.

Carrie Jonak, a research associate in Binder's laboratory, generated the preliminary data that helped secure the grant and will conduct much of the experimental work. The measure of success is straightforward: if treated Fragile X mice begin to resemble untreated normal mice—if their brain activity normalizes—the project will have demonstrated proof of concept. The pilot study won't directly test whether the mice learn or remember better. But Binder notes that if abnormal brain physiology corrects, cognitive and behavioral improvements would logically follow.

For Binder, the project represents a convergence of two separate scientific currents. He has spent years studying the neurobiology of Fragile X and epilepsy in animal models. Meanwhile, advances in protein engineering have made it possible to design molecules that can reach the brain. Neither field alone could have produced this work. "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."

The collaboration also reflects a shift in how academic research gets funded and conducted. Binder emphasized that as an academic laboratory, he would not normally have access to the kind of engineered therapeutics Bowen's FX Therapeutics has developed. The foundation grant made the partnership possible, bringing together university expertise in measuring brain function with private-sector advances in drug delivery. If the mice respond as hoped, the results could lay groundwork for human trials—and potentially offer the first targeted treatment for a disorder that has had none.