From Hope to Possibility: What a Gene Therapy Breakthrough Means for Kabuki Syndrome

Recently, The New York Times spotlighted a remarkable story: a baby named KJ became one of the first to receive a customized gene-editing therapy tailored to his rare genetic condition. This unprecedented treatment, built on decades of federally-funded scientific discoveries, was delivered just months after diagnosis—thanks to a powerful combination of urgency, innovation, and advocacy.

The story struck a deep chord within our Kabuki syndrome community. On KSF’s social media, your comments reflected both awe and pressing questions: What does this mean for Kabuki syndrome? Could this kind of breakthrough help our loved ones too?

The short answer is not yet, but this success shows us what is possible. In summary, here’s what we know and what we are doing to prepare our community: 

• The success of this treatment highlights a regulatory pathway that can deliver rare disease treatments on an accelerated timeline. 
• KJ’s treatment focused on the liver, an organ that is relatively easy to target with current delivery systems. In contrast, comprehensively treating Kabuki syndrome is much more challenging because it would require delivering therapy to the brain and/or multiple other organs. This is difficult due to the protective blood-brain barrier and the complex, multi-system nature of the condition. 
• Kabuki syndrome can be caused by many possible mutations across two large and complex genes. Personalized treatments for individuals’ unique mutations will require significant advances in delivery platforms, automation, and manufacturing scalability.  Additionally, not all types of mutations may be suitable for gene-editing (e.g. large deletions or insertions). 

A Future Within Reach

At KSF, we are laser-focused on advancing promising treatments for Kabuki syndrome, guided by expert advisors and powered by our global community. In 2024, we awarded our 2024 Discovery Grant to researchers exploring the use of a gene activator to restore normal levels of KMT2D. This type of progress prepares our community for rapid advancements in gene therapy development as technologies continue to evolve. 

We’re also engaging with researchers developing gene therapies for rare conditions similar to Kabuki syndrome. Adapting their work to include Kabuki syndrome could significantly accelerate treatment development.

Interested in more details? Keep reading for a deeper dive into the science:

A New Proof-of-Concept: Accelerated, Customized Rare Disease Treatments

KJ’s case proves that a pathway exists—from lab to FDA to bedside—for rare disease therapies to move quickly. The regulatory framework is in place in the United States and illuminates a path for future treatments. While KJ’s therapy was personalized for his specific condition, this kind of progress creates momentum for all rare disease research, including Kabuki syndrome.

The Science is Complex, and so is Kabuki Syndrome

KJ’s therapy targeted the liver, a relatively accessible and well-studied organ for gene therapy. Kabuki syndrome is a multisystem disorder. It affects nearly every cell type in the body, with some of the most significant impacts occurring in the brain. Delivering gene therapies to the brain—or systemically throughout the body—remains one of the biggest scientific challenges in the field. Safe and effective systemic delivery is in development, but routine clinical use is still several years away.

Kabuki syndrome is most commonly caused by mutations in the KMT2D or KDM6A genes, both of which are large and complex. Hundreds of unique mutations have been identified. This genetic diversity makes “one-size-fits-all” gene editing nearly impossible. Personalized gene editing addresses this issue by enabling the development of treatments tailored to an individual’s specific genetic mutation.  However, not all types of mutations (e.g. large deletions or insertions) may be eligible for gene-editing.

While personalized gene editing may someday be widely available, it currently faces steep obstacles in cost, time, and regulation. Widespread access to such personalized therapies will likely require major advances in delivery platforms, automation, and manufacturing scalability.

KSF is Moving Relevant Research Forward

At KSF, we are not waiting on the sidelines. Through our 2024 Discovery Grant, we are funding research into gene activators that could restore normal levels of KMT2D, potentially benefiting a broader segment of the Kabuki community than mutation-specific editing could. 

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 were awarded the Discovery Grant to study a gene-regulating tool called dCas9, which can activate or silence genes without altering DNA. Their project, called ZEPIKActive, 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. 

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.

Thank you for driving research with us. We’re in this together, and we’re just getting started.