Report: Assessing biological activity and in vivo efficiency of the epigenetic activator, 3R-ON

Posted by Friends of FSH Research on Dec 3, 2025

Report by Greg Block
See also Assessing biological activity and in vivo efficiency of the epigenetic activator, 3R-ON

For years, the search for an FSHD cure has focused on the "villain" of the story: the DUX4 protein. This nasty protein wakes up in muscle cells where it doesn't belong, acting like a wrecking ball. Most research aims to silence DUX4—essentially trying to slam on the brakes. At Histone Therapeutics, supported by Friends of FSH Research, we are taking an additive approach. Instead of just stopping the damage, we want to actively promote healing. We have developed a technology called 3R-ON. Think of it as a powerful "gas pedal" for your genes. Our goal for the first 6 months of the project was to determine if 3R-ON can activate two classes of genes. First, genes that put DUX4 back to sleep, and second, genes that wake muscle up to promote healing. Technologies like 3R-ON are new, and we need to understand them better before we use it as a medicine. For the first time, we were able show that 3R-ON is highly specific for its target gene, forming the basis of a future gene activating therapy unlike any other.