Circulating protein biomarkers identified in two independent clinical trial cohorts of glucocorticoid-naive Duchenne muscular dystrophy patients

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10506105" target="_blank" >RIV/00064203:_____/25:10506105 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/25:10506105

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=EsIV9V8snf" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=EsIV9V8snf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-025-23758-6" target="_blank" >10.1038/s41598-025-23758-6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Circulating protein biomarkers identified in two independent clinical trial cohorts of glucocorticoid-naive Duchenne muscular dystrophy patients

Popis výsledku v původním jazyce

Blood-accessible biomarkers offer promising insights into the pathogenesis of Duchenne muscular dystrophy (DMD) and other muscle diseases. Here, we quantified the relative abundance of 7,289 serum proteins using SomaScan proteomics in pre-treatment samples from 51 boys with DMD (aged 4 to &lt;7) and 13 healthy controls from the VISION DMD (VBP15-004) trial. An independent validation cohort of untreated DMD boys (aged 4 to &lt;8) from the FOR-DMD trial was also analyzed. Of the proteins screened, 26% and 15% were significantly elevated and decreased, respectively, in the serum of young DMD boys compared to controls (adjusted p-value &lt; 0.05). A high correlation (Spearman r = 0.85) in fold changes was observed between the two datasets. Many proteins with altered levels overlapped with known markers of muscle injury, inflammation, regeneration, and extracellular matrix remodeling. Selected biomarkers were queried in two published muscle mRNA and a muscle snRNAseq dataset in DMD biopsies. Novel factors involved in muscle regeneration and ECM remodeling were identified. This larger-scale, multi-clinical trial-based cohort study in untreated DMD boys substantially expands the catalog of circulating biomarkers, highlighting early-stage pathological processes. These findings can help identify new therapeutic targets and develop clinically actionable biomarkers to assess disease progression and response to therapies.

Název v anglickém jazyce

Circulating protein biomarkers identified in two independent clinical trial cohorts of glucocorticoid-naive Duchenne muscular dystrophy patients

Popis výsledku anglicky

Blood-accessible biomarkers offer promising insights into the pathogenesis of Duchenne muscular dystrophy (DMD) and other muscle diseases. Here, we quantified the relative abundance of 7,289 serum proteins using SomaScan proteomics in pre-treatment samples from 51 boys with DMD (aged 4 to &lt;7) and 13 healthy controls from the VISION DMD (VBP15-004) trial. An independent validation cohort of untreated DMD boys (aged 4 to &lt;8) from the FOR-DMD trial was also analyzed. Of the proteins screened, 26% and 15% were significantly elevated and decreased, respectively, in the serum of young DMD boys compared to controls (adjusted p-value &lt; 0.05). A high correlation (Spearman r = 0.85) in fold changes was observed between the two datasets. Many proteins with altered levels overlapped with known markers of muscle injury, inflammation, regeneration, and extracellular matrix remodeling. Selected biomarkers were queried in two published muscle mRNA and a muscle snRNAseq dataset in DMD biopsies. Novel factors involved in muscle regeneration and ECM remodeling were identified. This larger-scale, multi-clinical trial-based cohort study in untreated DMD boys substantially expands the catalog of circulating biomarkers, highlighting early-stage pathological processes. These findings can help identify new therapeutic targets and develop clinically actionable biomarkers to assess disease progression and response to therapies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Svazek periodika

15

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

39997

Kód UT WoS článku

001616350200022

EID výsledku v databázi Scopus

2-s2.0-105021941636