ArticleAnnals of clinical and translational neurology2026
Plasma EV Proteomics Identifies ECM Remodeling and Inflammatory Proteins LUM and C7 as Candidate Biomarkers in FSHD.
Article in Annals of clinical and translational neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveFacioscapulohumeral muscular dystrophy (FSHD) is one of the most debilitating and common muscular dystrophies. Despite its severity, no approved therapy exists for FSHD patients. However, several therapeutic candidates are currently under development, and some have recently entered clinical trials, marking the need for reliable biomarkers and outcome measures to monitor disease progression and treatment response in FSHD. To date, clinicians have relied primarily on validated functional and patient-reported outcome measures, while circulating molecular biomarkers remain unvalidated.
methodsHere, we investigated the plasma extracellular vesicle (EV) proteome to identify protein biomarkers that could be more reliably and conveniently used for FSHD prognosis, patient stratification for clinical trials and treatment response. In this study, we searched for EV protein biomarkers using plasma from 45 FSHD1 patients and 28 healthy controls distributed across two independent cohorts.
resultsUsing integrated, batch-corrected mass spectrometry analyses, we identified Lumican (LUM), along with several complement and extracellular matrix-associated proteins, as consistently upregulated EV proteins in FSHD. Additionally, LUM levels correlated with disease severity (FSHD-COM score; sex-adjusted Partial Pearson R: 0.454, p: 0.039) and other continuous clinical outcome measures (self-selected gait speed time; Pearson R: -0.485, p: 0.022 and timed up and go; Pearson R: 0.463, p: 0.034).
interpretationOur findings demonstrate that profiling circulating EV content in FSHD plasma can reveal EV protein biomarkers that warrant further validation in larger cohorts to assess their potential clinical relevance as minimally invasive surrogate molecular biomarkers for FSHD.
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