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Learn MoreHere, we describe the identification and characterization of p38 as a novel regulator of DUX4 expression in FSHD myotubes. By using multiple highly characterized, potent and specific inhibitors of p38/, we show a robust reduction of DUX4 expression, activity and cell death across FSHD1 and FSHD2 patient-derived lines. RNA-seq profiling reveals that a small number of genes are differentially expressed upon p38/ inhibition, the vast majority of which are DUX4 target genes. Our results reveal a novel and apparently critical role for p38 in the aberrant activation of DUX4 in FSHD and support the potential of p38/ inhibitors as effective therapeutics to treat FSHD at its root cause. SOURCE: Alejandro Rojas Fulcrum Therapeutics
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