Fragile X Syndrome Study Emphasizes Early Intervention

Research out of the University of Colorado (UC) suggests therapeutic interventions to treat neurodevelopmental disorders may be more effective if done during the early stages of brain development.

Published recently in The Journal of Neuroscience, the UC Skaggs School of Pharmacy study looked at Fragile X Syndrome (FXS), a pervasive neurodevelopmental disorder and a common cause of intellectual disability, autism, and anxiety disorders. 

“In order to stop the progression of neurodevelopmental disorders, it is important to identify how and when brain circuits are changing during development. Our study identifies when circuits are altered in addition to how brain circuits are corrected,” says the study’s senior author Molly Huntsman, PhD, associate professor at the UC Skaggs School of Pharmacy and Pharmaceutical Sciences.  “Currently, there are no approved or effective therapies targeting specific pathophysiology underlying the clinical manifestations of FXS. We’re hoping to provide answers for when and how to treat FXS to help with therapeutic options eventually.”

The work focused on the amygdala, the brain region where fear and anxiety are processed, and used a transgenic mouse model of FXS.   The team was able to identify potential causal circuit-level changes during a critical period of brain development susceptible to therapeutic intervention.

The results suggest that critical period plasticity in the amygdala is increased and may be shifted to earlier developmental timepoints, causing a “maladaptive” form of plasticity. The results also showed that fear-learning emerges in the brain during periods of increased plasticity and that early intervention ameliorates it.

“This is highly significant and addresses a critical barrier for understanding how circuits develop in a mouse model of autism and intellectual disability and even more important for therapeutic intervention-directed treatment options,” Huntsman says.

The researchers said future clinical trials should focus on human critical periods of development.