Study of the Week: A Potential New Treatment for Williams Syndrome

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.


This week’s study is…

Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams–Beuren syndrome

We previously published about this research in a story titled “Researchers Discover Potential Williams Syndrome Treatment” which can be found here. The study was originally published in the scientific journal eLife. You can read the full text of the study here

This research team was affiliated with the Universitat Pompeu Fabra – Barcelona Neuropharmacology Laboratory, in collaboration with several other universities.

What Happened?

Williams syndrome is a rare disease that is mostly associated with mild to moderate intellectual disability and hyper-sociality; however, it also causes potentially life-threatening cardiovascular problems. Treatment options for the syndrome are limited and no therapies that directly address the main traits of the disease are available. Therefore, there is an unmet medical need to develop more effective interventions for Williams syndrome.

In this study, researchers used a mouse model of Williams syndrome that mimics the genetic alteration that causes the disease in order to evaluate a potential treatment approach. The endocannabinoid system, which has importance for the function of the cardiovascular system and cognition, was chosen as a potential drug target by the scientists. This system, while not well understood, is known to be modifiable, principally by cannabis, but also by other pharmacological substances as well that act on the appropriate receptors.

The researchers found that there were alterations to the endocannabinoid system in the model mice, noting changes to the CB1 receptor more specifically. The team then began treating the mice with an investigational therapy called JZL184. This treatment has a mechanism of action designed to increase endocannabinoid levels. Previously, JZL184 had been shown to have anti-inflammatory effects on the brain. 

Over a ten day period of treatment, the mice showed modulation of their endocannabinoid systems and normalization of the some of the alterations seen in the CB1 receptor. This resulted in improvements in symptoms such as heart hypertrophy, hypertension (high blood pressure), hyper-sociability, and memory impairment. In control mice, the treatment had no effects, indicating that the approach had benefits specific to Williams syndrome.

The treatment modified gene expression; for example, in the heart, around 70 percent of the genes that were affected by Williams syndrome returned to normalized levels of expression. Overall, the researchers concluded that modifying the endocannabinoid syndrome could be key to more effectively treating Williams syndrome. 

About Williams Syndrome

Williams syndrome is a genetic disorder which can have a number of physical and mental impacts. It is most characterized by distinctive facial features and intellectual disability. The syndrome is linked to the microdeletion of some genetic material found on chromosome 7; only one chromosome of the pair is affected. Genes affected include LIMK1, CLIP2, ELN, GTF2IRD1, and GTF2I. Symptoms of Williams syndrome include heart defects, distinctive facial features, developmental delays, anxiety, phobias, low muscle tone, and failure to thrive. People with Williams syndrome are known for their friendly and sociable personality. They have an exceptional ability to empathize with others and have little fear of strangers. There is no cure for Williams syndrome; treatment focuses on addressing health concerns like heart defects; physical and behavioral therapy can also be beneficial. Patients often respond strongly to music, which can help with anxiety. To learn more about Williams syndrome, click here.

Why Does it Matter?

For physicians and scientists, the findings from this study are important in the field of genetic disorders in humans. More directly, the results also have encouraging implications for people that are impacted by Williams syndrome, as the mouse model of the disease was able to be treated successfully by modifying the endocannabinoid system.

These results give scientists a much clearer path to drug development in this rare disorder. Future research will aim to continue evaluating molecules that modify the endocannabinoid system that are closer to clinical development or that already have a medical application, as JZL184 is still far off from being approved for any use in humans.

“We are interested in testing other types of molecules that may be closer to clinical use and have a similar effect on the endocannabinoid system to the molecule we have used to see other therapeutic possibilities to find out to what extent we can reproduce the positive effects we have described.” – Andrés Ozaita, senior researcher, NeuroPhar, study co-author



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