University of Chicago and IDefine launch research program to develop Kleefstra syndrome treatment

The University of Chicago Department of Chemistry, in partnership with the advocacy organization IDefine – The Kleefstra Syndrome Foundation, is launching a targeted research program to develop a new potential therapeutic strategy for Kleefstra syndrome (KLEFS). Led by Principal Investigator Bryan Dickinson, the six-month project aims to address the root genetic cause of this rare neurodevelopmental disorder by using molecular tools to restore essential protein levels in the brain. 

Addressing the genetic mechanism of Kleefstra syndrome 

Kleefstra syndrome is a rare neurodevelopmental disorder resulting from haploinsufficiency of the EHMT1 gene. This genetic state causes intellectual disability, autism spectrum features, and developmental delays. Similar to Dravet syndrome caused by SCN1A haploinsufficiency, KLEFS represents an ideal candidate for translational upregulation therapy. 

To address this protein deficiency, the Dickinson lab will use their technologies for programmable translational activation of endogenous transcripts that have previously demonstrated success in targeting other transcripts, such as SCN1A. The Dickinson lab will develop EHMT1 targeted activators as a potential therapeutic strategy for Kleefstra syndrome. 

A foundation for future treatment 

Supported by a grant from IDefine, this collaboration represents a significant first step toward a potential future treatment for the Kleefstra community. The project focuses on translational activation, building a programmable platform that could eventually be adapted for other rare diseases characterized by similar genetic imbalances. Successful completion of this phase will provide the essential data needed to move toward subsequent milestones, such as testing neurons derived directly from patients and developing clinical delivery methods.