CSO Corner, Volume 14: Turning up the Volume on EHMT1

Hello fellow members of our KS family!

As you probably know, at its core, Kleefstra syndrome (KS) is caused by damage to one copy of the gene EHMT1. But people have two copies of EHMT1 (as with most genes)! Since every person with Kleefstra syndrome (KS) still has one perfectly healthy copy of the EHMT1 gene, one possible treatment path would be to find a way to “turn up the volume” on that single copy to compensate for the missing one.

I’ve often compared this to a situation where you have two car factories making cars, but then one factory has to shut down. What if you could run the other factory at twice the pace? Now you have the same total output of cars. Back in business!

Today, I am incredibly excited to announce that we are putting this strategy into high gear. Thanks to the overwhelming support of our “Turn Up the Volume” giving campaign, we are officially launching a new research partnership with the University of Chicago Department of Chemistry.

A Targeted Strike on EHMT1

This project is led by Principal Investigator Bryan Dickinson, whose lab specializes in synthetic biology—the science of creating new molecular tools to control the biological processes that drive human health. The Dickinson Lab will be using their cutting-edge “programmable translational activation” technology to target the EHMT1 gene directly.

If you think of the EHMT1 gene as a blueprint on an assembly line, this technology acts like a specialized “booster” that encourages the cell to read that blueprint more efficiently. The goal of this project is to eventually restore EHMT1 protein levels in the brain, addressing the root genetic cause of KS.

The First Step of a Larger Journey

It is important to understand that this initial project represents a significant first step toward a potential future treatment. Right now, we are focused on building and validating the programmable platform specifically for EHMT1.

If we achieve successful results in this initial phase, it will provide the essential data we need to expand the project. Further development would then move us toward subsequent milestones, such as testing the therapy in neurons derived directly from patients and developing the methods needed for clinical delivery.

From “Research Ready” to “Treatment Focused”

This partnership represents exactly what our “Turn Up the Volume” campaign was designed to do. For years, IDefine has worked to build the infrastructure—patient registries, model systems, etc.—to make us “Research Ready.” Now, we are pivoting to a “Treatment Focused” strategy, funding the specific scientific work that moves us from the laboratory bench toward the bedside.

By supporting this campaign, you are the catalyst for these solutions. This project with the Dickinson Lab is just the beginning. Our community’s generosity is allowing us to launch a multi-pronged attack on KS, diversifying our approach to maximize our chances of success.

Stay tuned—we have more exciting project announcements coming very soon as a direct result of this campaign!

Until next time,

Eric Scheeff, PhD 

IDefine Chief Scientific Officer