Research Supported by PWS Foundation to Examine Cause of Behavioral Problems, Possible Treatment

A grant winner’s research may help to advance a possible treatment of behavioral problems like temper outbursts in Prader-Willi syndrome patients. The treatment, an approved medication but not for PWS, works by modulating the levels of a neurotransmitter that might restore a balance in brain signals. 

Lauren Rice, a PhD scientist with the University of Sydney, Australia, was among eight winners of grants given by the Foundation for Prader-Willi Research earlier this year. Her $149,228 research award will support work into the potential treatment’s target, the neurotransmitter gamma-aminobutyric acid (GABA), and an early evaluation of its effectiveness.

Rice’s grant proposal was built on a study she and her team published in 2016. They reported that PWS patients with temper tantrums and other behavioral problems had significantly lower levels of the GABA neurotransmitter. The lower the GABA levels, the more likely a PWS patient was to exhibit such problems.

GABA acts in the brain to dampen or inhibit nerve signaling or impulses. A lack of GABA can lead to an imbalance between nerve signal firing (excitation) and their inhibition in the brain (called an E-I imbalance). 

Rice proposed that modulating GABA may restore the balance of neurotransmitters, and improving outburst behaviors in PWS patients.

Low GABA levels have also been identified in autistic people who exhibit temper outbursts, and in people with emotional problems such as major depressive disorder. Research to find GABA-modulators is ongoing in these medical conditions (autism and depression), and also in Angelman syndrome, fragile X syndrome, and Rett syndrome.

However, little attention has been given to GABA modulation in PWS treatment, underlying the importance of this grant. 

Researchers will use the GABA-modulating compound, acamprosate (sold under the brand name Campral), to evaluate its potential to normalize neurotransmitter balance in the brain. A brain-scanning technique called functional magnetic resonance imaging (fMRI) will be used to determine if neurotransmitter balance is restored in patients.

The team will also investigate if this acamprosate — an approved treatment for alcohol dependence — eases outburst behavior. 

If successful, Rice and her team will apply for a second year of funding to evaluate and test a larger  number of PWS patients. A larger study group will help to identify PWS patients who are most likely to respond to GABA modulation, and characteristics of patients best suited for future clinical trials.

In the long term, researchers hope to confirm if an excitation-inhibition imbalance exists in PWS patients, and establish a feasible approach for treating PWS-associated behaviors.

More information about this project is available in this video clip below by Theresa Strong, PhD, director of research program at FPWR: