12/02/2025
✨ A breakthrough years in the making ✨
When we launched the foundation four years ago, there were no animal models for KCNH1-Related Disorders. We were told that developing a cure would be impossible without one. “You need a KCNH1 mouse,” we were told. “You have to show you can cure the disease in a mouse before the FDA will let you try a new treatment in humans.”
So we went to Jackson Laboratories, a global leader in mouse-model development, and applied for a mouse model through their Rare Disease Translational Center. We got denied. We were crushed. But we rallied our amazing team of scientists to help us advocate, we persisted, and we finally convinced the lab that this was a worthwhile project to pursue. Because “no” isn’t an answer when your child’s future is on the line.
To make the model, they used gene-editing techniques to introduce Tristan’s exact mutation into the mice (basically the exact opposite of what we hope to do with our CRISPR gene-editing cure!). But it doesn't always work; these models take years to develop, and you can invest all of that time and effort and money, and then have nothing to show for it if the mice don't show a "phenotype," meaning they don't show symptoms of the disease.
So we waited…for over two years...while the mice were developed, bred for colony expansion, and then shipped off to a different lab to be studied.
And then a couple of months ago, we got some amazing news: the Tristan mice have a clear and robust phenotype!! Dr. Amy Shore, who has worked with many rare-disease mouse models, says she's never seen such a clear-cut behavioral phenotype: "I can take one look at the cages when they're undergoing tests and know--healthy, mutant, healthy, mutant." Tristan's mice show many of the same symptoms as Tristan: neurological abnormalities, motor deficits, growth deficits, and profound impairment in activities of daily living (for example, nest-building abilities).
These mice are sick, just like Tristan is sick, but Dr. Shore loves her furry little friends and takes great care of them. "We've seen how the emergence of a mouse model that recapitulates a disease can lead to an explosion of interest in the disease, significantly improving the understanding of disease mechanisms, and advancing the development of novel therapeutics," says Dr. Shore. "In the past few months, we've begun to identify strong physiological and behavioral impairments in Kcnh1-P560S mice, which we believe can be used to screen for new treatments for KCNH1 patients. We're grateful to have the opportunity to work on the KCNH1 mouse model, and hopeful that, with the introduction of this new disease model, the KCNH1 field will experience a similar trajectory of rapid advances to those seen with other rare genetic disorders."
And now, the moment that brings this story full circle: Jackson Laboratories, the lab that initially said no to developing this model because they didn't think it would be impactful, is now so impressed with these mice that they’ve told us they're going to start working on a gene therapy to screen in the KCNH1 mice!
This new milestone brings significantly increased costs, however. Screening treatments in mice is extremely expensive, but it's an essential step on the path to a cure. On this Giving Tuesday, please join us in supporting this critical next phase of research. Donate today to cure the Tristan mice, and bring us one HUGE step closer to life-changing treatments for KCNH1 kids!!
www.curekcnh1.org/donate
