In 2011, FSHD Global funded Genea Biocells to isolate the first embryonic stem cells from patients with FSHD. Genea has done an excellent job developing these lines, and sharing them with the research community. Here we are leveraging Friends of FSH Research's expertise in the development of assays for high throughput screening to support the creation of an engineered embryonic stem cell line that reports DUX4 activity.
This tool will be able to be used by researchers all over the world to perform basic research and screen for lead compounds that interfere with DUX4 expression. We have funded a number of screens previously, and these efforts have resulted in the identification of lead compounds.
There are only two ways to develop pharmacological drugs for things that reduce or inhibit DUX4. The first is to screen libraries of drugs, and the second is to design. To design you need to know the structure of DUX4, and we’re working on that (see Hideki Aihara’s grant we funded last cycle). In the meantime, we’ll screen libraries.
Screening a drug library is only as good as the assay that is being used. We have had success using a number of approaches: researchers have put DUX4 in to cancer cells for example, and looked for things that shut the artificial DUX4 down. But the thing is, if you’re artificially introducing DUX4 into cells, then you won’t detect drugs that may in fact prevent DUX4 from turning on in the first place.
If you want to do that, you have to do the experiment on a human cell from an FSHD patient. We’ve invested in those types of studies before, and those also generated potential leads. The problem with relying on human cells (in particular muscle cells) for screening, is they are difficult to grow, unpredictable, and tough to scale if you want to screen a lot of drugs (and believe me there are a LOT of drugs to screen in this world, ranging from libraries of FDA approved drugs to structure based libraries that look for classes of compounds).