Discovery Grant Awardees Share Multi-Symptom Improvement in Kabuki Syndrome Mice

The Kabuki Syndrome Foundation’s Discovery Grant is awarded annually to accelerate research that enables Kabuki syndrome therapeutic discovery. In 2023, $150,000 was awarded to the collaborative team of Dr. Hans Bjornsson, University of Iceland and Johns Hopkins Medicine; Dr. Karl Broman, University of Wisconsin; and Dr. Agnes Ulfig, University of Iceland for their project: Mapping genetic modifiers in Kabuki syndrome to identify novel therapeutic avenues. This research team is using Kabuki syndrome type 1 mice with different genetic backgrounds to discover new ways that Kabuki syndrome could be treated. Excitingly, the first phase of the project showed that Kabuki syndrome mice with certain genetic backgrounds had multi-symptom improvement.

Promising Preliminary Results

Individuals with Kabuki syndrome who carry the exact same mutation can exhibit striking differences in symptom severity, suggesting that genes ‘in the background’ could be modifying the condition’s effect. Identifying the background genes that may be modifying symptom severity, specifically those that result in less severe symptoms, could lead to new druggable targets for treatments.

To explore these genes, the research team started by creating mouse models of Kabuki syndrome type 1 that have the same mutation variant but different genetic backgrounds. In current Kabuki syndrome mouse models, each mouse is genetically identical, which is comparable to studying one individual person with Kabuki syndrome. 

After creating Kabuki syndrome mice with different genetic backgrounds, the researchers then evaluated their symptoms to pinpoint which mice showed the most symptom improvements. The first phase of the project revealed that Kabuki syndrome mice with certain genetic backgrounds showed multi-symptom improvement. Symptoms that improved included growth, hearing, immune system markers, blood sugar levels, and kidney formation.

Next Steps

Based on these results, the investigators will attempt to narrow down the background genes that are responsible for improving symptom severity and explore how they can be targeted for therapy. In addition to leading to the identification of potential treatment targets and novel therapeutic strategies, this study could also illuminate why there is such variability in Kabuki syndrome symptoms and severity. Stay tuned for updates on this two-year study funded by KSF.

Discover More

Teammember Dr. Bjornsson illustrated this project at our last annual conference; the recording is available to watch. Academic and industry investigators are welcome to explore all our grant opportunities.

This research wouldn’t be possible if it weren’t for the generous donations of our community. To help us fund more Discovery Grants and research to find treatments for Kabuki syndrome, please donate now.