Investigating a New Potential Target for Treatment in Prader-Willi Syndrome

Funding Summary

Dr. Rice and colleagues have shown that there is a decrease in GABA (a compound that helps turn brain activity off) in the brains of individuals with PWS, and this is associated with emotional problems, including a tendency for temper outbursts.  In this project, the team will use brain imaging (fMRI) to examine whether a GABA-modulating drug (Acamprosate) can normalize the balance of neurotransmitters in the brain, and if this results in improved behavior.

This study will provide fundamental information about PWS brain connectivity and evaluate a potential treatment for challenging PWS behavior. 

* Funded by the Foundation for Prader-Willi Research - Canada

Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.  

Watch the full webinar describing the 8 research projects funded in this grant cycle here. 

Lay Abstract

Behavior disturbance increases the cost and stress associated with caring for a person with PWS. Despite this, there are currently no effective treatments for the core behavior problems of PWS. Using a novel and non-invasive imaging technique, we found that people with PWS and severe behavior disturbance had significantly lower brain gamma-aminobutyric acid (GABA) levels than typically developing controls and people with PWS with low rates of behavior disturbance. GABA is the major inhibiting neurotransmitter in the brain, meaning it helps turn brain activity off. The behaviors that correlated most highly with low GABA in people with PWS were autism-like behaviors and emotional problems (temper outbursts and depressive symptoms). Consistent with these findings, research has shown the people with autism, and people with major depressive disorder also have reduced brain GABA levels. Many studies are now working to identify a GABA modulator that can restore the altered GABA system in autism and depression. Similar work is being conducted in Angelman syndrome, Fragile X syndrome and Rett syndrome. Unfortunately, there is currently little interest from pharmaceutical companies in trialing these GABA modulators in PWS, primarily due to a lack of information about the GABA system in PWS.

We aim to address this issue by examining whether people with PWS show the same unique brain response to a GABA modulator that has been found in autism. If we find that they do, then this then this will help identify a new potential target for treatment in PWS. These findings will also attract the attention of pharmaceutical companies that are currently investing in clinical trials of GABA in autism and other developmental disabilities. If successful, we will apply for a second year of funding to increase the PWS sample size which will allow us to identify whether there is a subgroup of people with PWS who are most likely to respond to GABA modulators. This information could then be used to identify responders for future clinical trials. There are a number of available potential GABA modulators which could then be trialed to see if they improve behavior in some individuals with PWS.