Over the years, researchers have relied on the generosity and courage of our patient community who volunteer for important clinical studies in FSHD. Many of you have given your valuable time, undergone complicated muscle strength test, filled out endless questionnaires and even volunteered to give muscle biopsies so scientists can better understand FSHD disease progression. With regard to muscle biopsies, although many now cause minor discomfort, you may well wonder why they are required for some FSHD clinical trials.
The reason is that many of the new treatments being developed for FSHD take aim at the DUX4 gene. When DUX4 switches on, it acts like a “dirty bomb” that unleashes a shower of other genes that damage and ultimately kill muscle cells. DUX4 is like the fuse that triggers a chain reaction of toxic events. To prove that a proposed treatment “engages the target” – or in this case blocks DUX4 in order to defuse the bomb – any anti-DUX4 drug has to be shown to actually shut down the expression of the DUX4 gene. Right now, the only way to prove this is by directly analyzing muscle cells from a patient, before and after the drug is given. And this is why muscle biopsies continue to be necessary.
What if there were another way to show that the drug has engaged its target, one that doesn’t require taking small pieces of your muscle? Our biomarker initiative is aimed at solving this question. Since DUX4 itself is difficult to measure, researchers typically monitor the chain reaction of toxic events caused by DUX4 to track its activity. This shower of genetic shrapnel unleashed by DUX4 results in chemical changes—or biomarkers—that can be measured in patients’ muscle. It is very likely that some of these markers get released into the bloodstream and could be detected with sensitive tests. This relationship has to be validated by analyzing muscle biopsies and blood samples from many patients and showing that there is a strong correlation between DUX4 expression in muscles with the chemical signature.
Once scientists have agreed that this signature is a reliable biomarker, we will work with companies to develop an assay, or test, to measure it. Having this biomarker assay will make clinical research and trials faster, cheaper, and more accurate. And this will be as easy as a routine blood test.