Characterization of the Endocannabinoid System and its Modulation as a Therapeutic Avenue for Fragile X Syndrome
Francois Corbin, PhD
Benoit Laurent, PhD
Olivier Dionne, PhD
FRAXA Postdoctoral Fellow
University of Sherbrooke
2023-2024 Grant Funding: $100,000
Cannabidiol (CBD) has been in the news as a potential treatment for Fragile X syndrome, and a clinical trial is underway. But how much is known about how it works?
This team will methodically investigate the Fragile X brain's response to CBD using a human model of neurons.
Individuals with Fragile X syndrome (FXS) do not produce a protein, FMRP, which leads to abnormal brain development and learning difficulties. Cortical hyperexcitability is currently recognized by the scientific community as the core deficit in the brain of both Fragile X patients and animal models. Several mechanisms contribute to cortical hyperexcitability, including mGluR5 hyperactivity which led to Novartis and Roche clinical trials 10 years ago.
More recent findings suggest that an alteration of the endocannabinoid (eCB) system also contributes to this deficit. Cannabidiol (CBD), a non-hallucinogenic component of the cannabis plant, can modulate the eCB system and has shown promising results in recent Fragile X clinical trials.
The purpose of this project is to characterize the eCB system more thoroughly in Fragile X syndrome using a human model of neurons. Using this model, we seek to investigate the ability of CBD and other drugs targeting this system to correct the core deficit of the syndrome. This project may allow us to identify new therapeutical strategies to change the natural course of the syndrome.