Oligodendrocytes: a Potential Route to Treat Fragile X Syndrome
Lida Zoupi, PhD
Principal Investigator
Laura Oliveira, PhD
FRAXA Postdoctoral Fellow
University of Edinburgh
Scotland
2025-2026 Grant Funding: $100,000
Summary
This project takes aim at an often-overlooked part of the Fragile X brain: oligodendrocytes — support cells that produce myelin, the insulation that helps nerve signals travel efficiently. Without healthy myelin, brain communication is disrupted.
The Zoupi Lab has shown that myelin and oligodendrocytes are abnormal in Fragile X models, but it’s unclear if they actually cause the brain dysfunction or are just a side effect. To find out, Dr. Laura Oliveira will use a new mouse model with FMR1 deleted only in oligodendrocytes and test whether restoring their function with medication can improve brain activity.
If successful, this research could lead to a new treatment strategies that target brain support cells, not just neurons, in Fragile X.
The Science
by Dr. Laura Oliveira
Our brains consist of nerve cells (neurons) and surrounding cells (glia) that constantly communicate. Insulation around neurons is crucial for the fast transmission of signals across the brain, which is essential for optimal brain function. The type of glial cell called an oligodendrocyte is responsible for producing this insulation (myelin) and for supporting nerve cells to function efficiently.
Imaging studies in children with Fragile X syndrome (FXS) have identified changes in brain structure linked to alterations in myelin. However, we do not know if and how these lead to abnormal function of nerve cells in FXS.
A previous study in the Zoupi lab showed that deficits in oligodendrocytes lead to alterations in myelin both in a rat model of FXS and in human-derived FXS oligodendrocytes. This raises the following questions:
- Do oligodendrocyte-specific deficits contribute to neuron dysfunction in FXS?
- If so, can impairments in the function of neurons be restored by targeting oligodendrocytes?
I will use a novel mouse model where the gene which is altered in FXS (Fmr1) is selectively deleted from oligodendrocytes to test if changes in oligodendrocytes alone can lead to the neuron dysfunction seen in FXS. I will also test whether targeting oligodendrocytes pharmacologically can restore neuronal impairments seen in a mouse model of FXS.
Overall, this project will reveal whether targeting oligodendrocytes can provide a novel treatment avenue for Fragile X syndrome.
