Longitudinal measures of RNA expression and disease activity in FSHD muscle biopsies

ABSTRACT: Advances in understanding the pathophysiology of facioscapulohumeral dystrophy (FSHD) have led to the discovery of candidate therapeutics and it is important to identify markers of disease activity and progression to inform clinical trial design. For drugs that inhibit the expression of DUX4, measuring DUX4 or DUX4 target gene expression might be an interim outcome measure of drug activity, however, only a subset of muscle biopsies in FSHD show evidence of DUX4 expression. Our prior study showed that MRI T2-STIR positive muscles had a higher probability of showing DUX4 expression than muscles with normal MRI characteristics. In the current study, we performed a one-year follow-up assessment of the same muscle with repeat MRI and muscle biopsy. There was very little change in the muscle MRI characteristics over the one-year period and, similar to the initial evaluation MRI T2-STIR-postive muscles had a higher expression of DUX4 regulated genes, as well as genes associated with inflammation, extracellular matrix, and cell cycle. Compared to the initial evaluation, overall the level of expression in these gene categories remained stable over the one-year period, however, there was some variability for each individual muscle biopsied. We pooled the data from both the initial and one-year follow-up evaluations and identified several subgroups based on gene expression, as well as a set of genes that distinguished all of the FSHD samples from the controls that include DUX4-regulated genes, inflammatory immune genes, and cell cycle control genes. These candidate markers of disease activity need to be validated on independent datasets, but will hopefully be useful in studies of disease progression and response to therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE140261 | GEO | 2020/02/25

REPOSITORIES: GEO