The discovery made by an international team of researchers led by a scientist at Fred Hutchinson Cancer Research Center could lead to a biomarker-based test for diagnosing facioscapulohumeral muscular dystrophy (FSHD), and the findings have implications for developing future treatments as well as for cancer immunotherapies in general.
The work established a viable roadmap for how the expression of the DUX4 gene can cause FSHD.
Corresponding author Stephen Tapscott, M.D., Ph.D., a member of the Hutchinson Center's Human Biology Division said that whether this is the sole cause of FSHD is not known; however, the latest findings "are about as strong of evidence as you can get" of the genetic link.
Tapscott and colleagues sought answers to the questions about what the DUX4 protein does both normally in the body and in the FSHD disease process.
In the latest study, they identified that the DUX4 protein regulates many genes that are normally expressed in the male germ line but are abnormally expressed in FSHD muscle. Germ line cells are inherited from parents and passed down to their offspring.
"This study is a significant step forward by solidifying that the DUX4 transcription factor causes this disease, while offering a number of viable mechanisms for why the muscle is damaged," Tapscott said.
Transcription factors are tools that cells use to control gene expression. Genes that are "turned on" in the body are "transcribed," or translated, into proteins.
Now that scientists know that targets for DUX4 are expressed in skeletal muscle, an antibody- or RNA-based test could be developed to diagnose FSHD by examining muscle tissue from a biopsy, Tapscott said.
Such biomarker-based tests also could be used to determine how well new treatments are working to suppress FSHD.
The study has been published in the journal Developmental Cell.