MRI-guided biopsy shows promise for clinical trials

Image courtesy of GE.
Method may predict DUX4 activity in patients’ muscles

A central tenet of modern FSH muscular dystrophy research is that the muscle damage in this disease is caused by a gene called DUX4. Normally silent in adult skeletal muscle, DUX4 is expressed through a genetic aberration and triggers a shower of toxic molecular events. This idea lies behind a flurry of efforts to treat FSHD through drugs and gene therapies designed to repress DUX4.

But proving that DUX4 causes damage in actual patients has been no easy task. In a major step forward, researchers from the University of Washington and the University of Rochester published a study showing that pathologic changes in patients’ muscles, as seen under a microscope, are correlated with patterns of genes that are switched on when DUX4 is expressed.

The bicoastal team accomplished this discovery by collecting tiny bits of patients’ muscles guided by magnetic resonance imaging (MRI). Prior studies had suggested that MRI can detect various stages of the disease process. “Dystrophic” muscles were filled with fat and scar tissue, which showed up as bright spots when the MRI was tuned to detect fat. On the other hand, some healthy-looking muscles looked abnormal when the MRI was tuned to detect water. Researchers had suspected that the excess water in these muscles resulted from inflammation.

These prior MRI studies hinted that inflamed muscles might have DUX4 activity leading to dystrophy. Data from the new study are consistent with this hypothesis and point the way to designing clinical trials. MRI-guided muscle biopsy could, in theory, show that a drug is actually repressing DUX4 in patients, while a sequence of MRI images taken after treatment might reveal whether the drug is slowing or stopping the damage to muscles.

Much work still remains before this method can be considered valid. The researchers would like to study the same group of patients over time to gain a fuller understanding of how the disease progresses.

Most importantly, scientists need to replicate these findings to discern how reliable this method is over repeated use in diverse groups of patients before the approach can be considered “industrial strength” and ready to use in a clinical trial. Those studies are now going on, with results expected in about a year.


Wang LH, Friedman SD, Shaw D, Snider L, Wong CJ, Budech CB, Poliachik SL, Gove NE, Lewis LM, Campbell AE, Lemmers RJFL, Maarel SM, Tapscott SJ, Tawil RN. MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD. Hum Mol Genet. 2019 Feb 1;28(3):476-486.


One response to “MRI-guided biopsy shows promise for clinical trials”

  1. Has the insterstitial fluid been tested for molecular remnants of DUX4 activity? I believe Dan Miller has reduced the necessary biomarkers to four, and while invasive this approach would be less damaging.

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