Meeting report: the 2020 FSHD International Research Congress
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MEETING REPORT
Open Access
Meeting report: the 2020 FSHD International Research Congress Michael Kyba1 , Robert J. Bloch2, Julie Dumonceaux3, Scott Q. Harper4,5, Silvère M. van der Maarel6, Francis M. Sverdrup7, Kathryn R. Wagner8,9, Baziel van Engelen10 and Yi-Wen Chen11,12*
Keywords: Facioscapulohumeral muscular dystrophy, Muscular dystrophy, Meeting Facioscapulohumeral muscular dystrophy (FSHD) spent many years in a wilderness of unexplained genetic mechanism while other monogenic muscular dystrophies saw rapid progress on genetic mechanism soon after their corresponding genes were discovered, with current interventions developed based on these discoveries. While it is now the consensus of the field that aberrant expression of the DUX4 transcription factor is ultimately responsible for FSHD, the linkage of such expression to muscle degeneration through a specific pathological mechanism has proven elusive, a concerning situation for many developing therapies. The 2020 Facioscapulohumeral Muscular Dystrophy (FSHD) International Research Congress, held online, June 25–26, and involving 280 registered participants from 5 continents, revealed strides to bridge this gap, as well as steps toward therapy, including the initiation of the first clinical trial specifically targeting DUX4 expression.
Session 1: discovery research and models Understanding which cell type DUX4 acts in, and what its pathological effects are in that cell type, benefit from investigating pathology at multiple levels, and advances highlighted in this area ranged from cell to tissue to system-wide. Major findings include the potential role of DUXA in sustaining DUX4 effects, DUX4 effects on * Correspondence: [email protected] 11 Department of Genomics and Precision Medicine, The George Washington University, Washington, DC 20052, USA 12 Center for Genetic Medicine Research, Children’s National Research Institute, Washington, DC 20010, USA Full list of author information is available at the end of the article
muscle regeneration, novel circulation biomarkers, and a fish model for studying DUX4 effects. Because DUX4 is known to impair myoblast differentiation, and has been proposed to have effects on satellite cells, Peter Zammit (Kings College, London) investigated to what extent regeneration is occurring in FSHD muscle. PAX7 and DUX4 are known to have mutually inhibitory effects on gene expression, suggesting that the expression of DUX4 in satellite cells would reduce myogenic potential. Consistent with this, myogenic and satellite cells in murine models of FSHD express DUX4. Muscle regeneration in mice carrying a DUX4-βgal reporter gene and challenged with cardiotoxin shows upregulation. PAX7+ satellite cells show similar upregulation. This suggests that DUX4 expression accompanies the activation of the myogenic program in muscle stem cells. Transcriptomic studies of regenerating healthy and FSHD muscle show that myogenic gene expression is elevated in FSHD muscles compared to controls. At the protein level, assayed by immunofluore
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