Driving the Kabuki Syndrome Research Agenda

The Kabuki Syndrome Foundation has committed an additional $66,500 to expand our Unravel Biosciences drug repurposing study to include participants with Kabuki syndrome type 1 (KS1), building on our initial work on Kabuki syndrome type 2 (KS2).

Unravel’s proprietary bioinformatics platform will analyze RNA sequencing data from participants with KS1 to identify disrupted biological pathways and predict compounds that may have therapeutic effects for Kabuki syndrome. The addition of KS1 participants will enrich our dataset, helping researchers understand the similarities and differences between KS1 and KS2, while strengthening the Kabuki syndrome therapeutic pipeline.

Read more about the expanded drug repurposing study.

We have granted $66,500 to Unravel Biosciences and recruited 20 research participants with Kabuki syndrome type 2 (KDM6A) for this drug repurposing study. This project aims to discover potential treatments for Kabuki syndrome type 2 using Unravel’s proprietary bioinformatics platform.

By analyzing RNA data from the nasal swabs of participants and matched controls, Unravel will identify potential therapeutic targets and predict compounds - including FDA-approved and other compounds - capable of restoring disrupted RNA function.

Read more about this first-ever Kabuki syndrome type 2 drug screen.

We granted $45,132.96 to Dr. David Genevieve, French National Institute of Health and Medical Research (INSERM); Farida Djouad, INSERM; Jean-Christophe Andrau, Institute of Molecular Genetics of Montpellier; and Kyle Fink, University of California Davis for their study: ZEPIKActive.

They aim to study a gene-regulating tool called dCas9, which can activate or silence genes without altering DNA. Their project is utilizing zebrafish models of Kabuki syndrome to test how well dCas9 can target and activate the KMT2D gene, as well as to assess its safety. If successful, this approach can be adapted for human cells and testing in animal models before moving toward human clinical trials. 

This gene-targeting therapy could potentially benefit a broader segment of the Kabuki community than mutation-specific gene editing could. 

By investing in this kind of research today, we’re ensuring our community is ready to benefit from future rapid advancements in gene-targeting technology. Read more.

We have granted $45,000 to Dr. Jacqueline Harris, Kennedy Krieger Institute and Dr. Patricia Cogram, GeN, to determine the optimal dose of BHB supplement needed to improve cognitive symptoms in mouse models of Kabuki syndrome. We look forward to sharing the results of this study in 2025.

Research from Dr. Hans Bjornsson’s group has demonstrated that the ketogenic diet can rescue memory deficits in a Kabuki syndrome mouse model. This benefit is likely due to BHB, a ketone body produced during ketosis, which enhances the function of the Kabuki protein by inhibiting a competing protein. Recognizing that highly restrictive diets can be challenging, we are exploring the use of exogenous BHB supplements, commonly used by athletes, to boost BHB levels.  However, these supplements’ effects can be short-term, causing fluctuating BHB levels. This study will evaluate whether these supplements can deliver similar cognitive benefits as sustained ketosis achieved through the ketogenic diet. 

This award was part of our 2024 Discovery Grant.

Watch an Update from Dr. Harris

Dr. Olaf Bodamer and his team at Boston Children’s Hospital are screening existing or FDA-approved drugs that could be repurposed to treat Kabuki syndrome. They aim to identify drugs that increase KMT2D and/or KDM6A protein levels, which are believed to improve Kabuki syndrome symptoms. 

We have granted $110,000 to advance their lead candidate via our Therapy Development Fund and look forward to sharing results in 2026. Boston Children’s Hospital is also home to the Roya Kabuki Program, the multi-disciplinary clinic for Kabuki syndrome established by the Zegna Family, who serve on our Board of Directors.

The winners of our 2024 Discovery Grant will receive $75,000 over two years to use to test existing drugs that could treat Kabuki syndrome in mouse models. The team includes: Dr. Patricia Cogram and Dr. Emilio Kropff, GeN; and Dr. Jacqueline Harris, Kennedy Krieger Institute. Dr. Harris will help prioritize the repurposed candidate from the Unravel Biosciences study and GeN, an academic contract research organization, will test these candidates in mice with Kabuki syndrome, focusing on both molecular and behavioral outcomes. The goal is to identify at least one repurposed drug that shows promise as a therapeutic candidate for Kabuki syndrome and potentially uncover new therapeutic targets for future research.

This drug screen complements the drug screen project at Boston Children’s Hospital. One of the differences with PATH 4K is that KSF will retain control over the data, timeline, and decisions.

To better understand how vafidemstat may affect Kabuki syndrome symptoms, we have granted $300,000 through our Therapy Development Fund to test vafidemstat in a mouse model of Kabuki syndrome. This study, conducted at a contract research organization (CRO), will assess the compound’s pharmacological and molecular impacts, as well as its effects on learning and memory through functional and behavioral evaluations. We look forward to sharing the results of this testing in 2025.

Vafidemstat is developed by Oryzon; in 2024, this company needed to reprioritize their drug development pipeline, which included postponing the planned Kabuki syndrome clinical trial. As a community, we have an active role in pushing this potential treatment forward. Oryzon estimates that $5-6 million in funding from KSF could kickstart a Phase 1/2 clinical trial. To de-risk an investment of this size, and based on input from our Industry Advisory Board, we are funding this preclinical work to validate vafidemstat’s potential for Kabuki syndrome in a mouse model. If the data is positive, it will strengthen our confidence as a community in moving forward with fundraising for vafidemstat clinical trials.

Additionally, this mouse colony will remain available for future therapeutic studies. This resource allows KSF to quickly initiate new preclinical research, empowering our community to accelerate treatment development.

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Two grants of up to $250,000 will be awarded to accelerate the development of treatments for Kabuki syndrome. The Therapy Development Fund is designed to bridge the critical gap between lab and patients, by funding research that can meaningfully advance potential treatments from proof-of-concept to clinical trials. 

Application Details

GestaltMatcher is an innovative AI program designed to recognize condition-specific facial features, like those seen in Kabuki syndrome. The diagnostic process for a rare disease can be lengthy; this AI aims to shorten the timeline. Having an accurate of diagnosis of Kabuki syndrome can significantly improve patient’s quality of life and enables clinical trial participation. Additionally, this AI can help more people find their diagnosis faster – helping us create more momentum and more resources for treatment development.

Discover the Power of Diagnosis

We’re thrilled to welcome four biotech and pharmaceutical leaders to our new Industry Advisory Board. As we work to advance treatments, their collective expertise is invaluable.

Meet all our Advisors

Based on feedback from our advisors, we designed and facilitated the first monthly lab meeting of Kabuki syndrome investigators. These meetings create new opportunities for knowledge exchange and collaboration and are open to all researchers and clinicians with an interest in Kabuki syndrome.

More Details for Researchers

The KSF Discovery Grant awards up to $150,000 over two years to a collaborative team who aims to identify or develop endpoints/biomarkers/outcome measures AND/OR potential druggable targets for therapeutic development. Academic and industry partnerships can be facilitated by KSF.

Explore the Application

Kabuki Count is the global Kabuki syndrome census and contact registry, led by KSF in partnership with 11 other global Kabuki syndrome organizations. Kabuki Count ensures we can notify potentially eligible patients for future studies and clinical trials.

Explore our Insights and Growth

This year’s research conference for families, clinicians, and researchers focused on the launch of The Kabuki Syndrome Outcome measures and biomarkers Consortium (KSOC). Within 24 hours, we recruited over 100 families to KSOC, exceeding our initial recruitment goal of 90. Watch the conference on YouTube, featuring the KSOC experts, participants, and more.

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Dr. Margaret Adam, Seattle Children's Hospital
Dr. Olaf Bodamer, Boston Children's Hospital
Dr. Jacqueline Harris, Kennedy Krieger Institute
Dr. Evdokia Anagnostou and Dr. Rosanna Weksberg, Holland Bloorview Kids Rehabilitation Hospital

The Kabuki Syndrome Outcome measures and biomarkers Consortium (KSOC) is a new collaborative clinical research study created, funded, and led by the Kabuki Syndrome Foundation to develop tools that can help take potential therapeutics to human clinical trials. Currently, there are no Kabuki syndrome-specific tools, like biomarkers, that can measure the impact of a therapeutic in a clinical trial. We are funding a total of 150 families to travel to one of four locations in North America to see an expert and participate in this research study. Discover how KSOC unlocks more possibilities for treatments.

Explore KSOC

Dr. Hans Bjornsson, University of Iceland, Johns Hopkins
Dr. Karl Broman, University of Wisconsin
Dr. Agnes Ulfig, University of Iceland

The 2023 KSF Discovery Grant was awarded to this innovative team to uncover why symptoms and severity can vary so greatly between people diagnosed with Kabuki syndrome by developing mouse models of Kabuki syndrome with different genetic backgrounds. This research could lead to the identification of potential therapeutic targets and the development of novel therapeutic strategies. Watch Dr. Bjornsson illustrate this two-year project at our 2023 Research Conference.

Grant Opportunities

This virtual event fostered collaborations and encouraged scientific knowledge-sharing by enabling Kabuki syndrome experts to gather and discuss their latest findings. From this event, we built new collaborations that have helped accelerate the timeline to treatments.

View the Symposium Summary

We’re delighted to announce the addition of Dr. Bruce Bloom and Dr. Clara Tang as Chief Scientific Officer and Director of Research, respectively. With over 20 years of combined experience in rare drug research, their expertise will significantly contribute to the development of the roadmap to treatments for Kabuki syndrome.

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Our virtual conference featured flash-talks from key institutions, deep dives into issues that deeply impact families, and tools for educational settings. We highlighted the pivotal role of families and patients in clinical trial design and how we are collaboratively building the pipeline to clinical trials in Kabuki syndrome. Dive into our conversations with experts and adults with Kabuki syndrome.

View Conference Videos

Dr. Jacqueline Harris, Kennedy Krieger Institute, was granted funds to support research at that will accelerate cross-institutional clinical trial readiness. She is developing and leading the validation of a battery of neurologic and neurodevelopmental outcome measures for use in future clinical trials in Kabuki syndrome. Research will include testing batteries that focus on the visuospatial perception and anxiety symptoms of anxiety and include those affected by Type 1 (KMT2D) and Type 2 (KDM6A) and an age range of infant to adult.

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16 Kabuki syndrome researchers and clinicians, 7 adults with Kabuki syndrome, and 8 patient advocacy leaders from around the world illustrated the current state of the Kabuki syndrome research landscape and the shared vision of a brighter future.

Watch the Conference

Our Advisors offer valuable guidance on our strategy, both as investigators and expert clinicians. Their combined expertise assists us in navigating the complexities of therapeutic development, and their work helps us advance promising candidates to clinical trials.

Meet our Advisors