The Opportunity: Kleefstra Syndrome
as a Target for Treatment Development
Kleefstra syndrome (KS) is a rare neurodevelopmental disorder caused by haploinsufficiency of a single gene: EHMT1 (Euchromatic histone-lysine N-methyltransferase 1).
The EHMT1 gene codes for an enzyme that plays a crucial role in epigenetics by methylating histone H3 at lysine 9, which helps regulate gene expression. This process is fundamental to neuronal development and function, making it a highly actionable target.
- KS has been extensively studied for two decades, leading to a deep understanding of the fundamental aspects of the syndrome on a cellular and biochemical level.
- KS is primarily a neurodevelopmental disorder, with developmental delay, intellectual disability, and autism as the most universal manifestations.
- Prevalence is approximately 1 in 25-35K people, leading to an expected population in the USA alone of ~10K patients.
- The Unmet Need is Substantial: KS currently has no available targeted treatments.
A Comprehensive Toolbox for Kleefstra Syndrome Research
Preclinical Models
A suite of established and validated research models are available to screen and validate any potential treatment.
iPSCs & Patient-Derived Cell Lines
IDefine has created patient-derived iPSCs and corresponding isogenic KS models and controls, available to ship immediately. KS neurons show a well-established phenotype for validation.
Order Our iPSC Lines →Organoid Models (In Progress)
Projects to develop and phenotype KS organoids are ongoing at UCSD and UCLA. Researchers can soon look forward to an established phenotype for screening treatments.
Contact IDefine for updatesMouse & Fly Models
Characterized mouse models enabling *in vivo* studies (RIKEN) and *Drosophila* fly models showing clear phenotypic rescue are available.
Order Mouse Models (RIKEN) →Patient Biosamples & Clinical Data
Simons Searchlight (Biosamples & Data)
International program collecting detailed medical histories, survey data, and **matched patient blood samples** for KS. The community is rapidly growing.
Explore KS in Simons Searchlight →COMBINEDBrain Biorepository
Houses KS blood samples coupled to survey data, along with control specimens. It is also the home of our iPSC lines.
Access Sample Spreadsheet →Rare-X & Citizen Health Data Platforms
Real-world data and patient insights collected through these platforms, with approximately 300 total enrolled KS patients providing a range of survey-based data.
Prospective Natural History Studies
Two prospective studies have been undertaken for KS—one completed and nearing publication, and one ongoing (in partnership by IDefine and Boston Children's Hospital).
A Collaborative Global Community
Research on Kleefstra Syndrome is supported by a dedicated network of patient advocacy groups, clinics, researchers, and academic consortia. We foster a collaborative environment and can connect you with key opinion leaders and the patient community to ensure your research is impactful and aligned with patient needs.
Our Key Partners in Research Readiness:
Getting Started with KS Resources
Your next breakthrough in neurodevelopmental disorders could start here. The resources are available now, and our community is ready to support you.
Explore the Resources
Follow the links above to our partners' websites to learn more about specific datasets and how to request access.
Explore Toolbox ↑Contact Our Liaison
Have a specific question or need help navigating the resource landscape? Reach out to our scientific liaison for personalized guidance.
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