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Article ; Online: Serum proteomic profiling reveals fragments of MYOM3 as potential biomarkers for monitoring the outcome of therapeutic interventions in muscular dystrophies.

Rouillon, Jérémy / Poupiot, Jérôme / Zocevic, Aleksandar / Amor, Fatima / Léger, Thibaut / Garcia, Camille / Camadro, Jean-Michel / Wong, Brenda / Pinilla, Robin / Cosette, Jérémie / Coenen-Stass, Anna M L / Mcclorey, Graham / Roberts, Thomas C / Wood, Matthew J A / Servais, Laurent / Udd, Bjarne / Voit, Thomas / Richard, Isabelle / Svinartchouk, Fedor

Human molecular genetics

2015  Volume 24, Issue 17, Page(s) 4916–4932

Abstract: Therapy-responsive biomarkers are an important and unmet need in the muscular dystrophy field where new treatments are currently in clinical trials. By using a comprehensive high-resolution mass spectrometry approach and western blot validation, we found ...

Abstract Therapy-responsive biomarkers are an important and unmet need in the muscular dystrophy field where new treatments are currently in clinical trials. By using a comprehensive high-resolution mass spectrometry approach and western blot validation, we found that two fragments of the myofibrillar structural protein myomesin-3 (MYOM3) are abnormally present in sera of Duchenne muscular dystrophy (DMD) patients, limb-girdle muscular dystrophy type 2D (LGMD2D) and their respective animal models. Levels of MYOM3 fragments were assayed in therapeutic model systems: (1) restoration of dystrophin expression by antisense oligonucleotide-mediated exon-skipping in mdx mice and (2) stable restoration of α-sarcoglycan expression in KO-SGCA mice by systemic injection of a viral vector. Following administration of the therapeutic agents MYOM3 was restored toward wild-type levels. In the LGMD model, where different doses of vector were used, MYOM3 restoration was dose-dependent. MYOM3 fragments showed lower inter-individual variability compared with the commonly used creatine kinase assay, and correlated better with the restoration of the dystrophin-associated protein complex and muscle force. These data suggest that the MYOM3 fragments hold promise for minimally invasive assessment of experimental therapies for DMD and other neuromuscular disorders.
MeSH term(s) Adolescent ; Adult ; Animals ; Biomarkers ; Blood Proteins/metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Connectin/blood ; Connectin/metabolism ; Creatine Kinase ; Disease Models, Animal ; Humans ; Mass Spectrometry ; Mice ; Mice, Inbred mdx ; Muscular Dystrophies/blood ; Muscular Dystrophies/metabolism ; Muscular Dystrophies/therapy ; Muscular Dystrophy, Duchenne/blood ; Muscular Dystrophy, Duchenne/metabolism ; Proteomics/methods ; Treatment Outcome ; Young Adult
Chemical Substances Biomarkers ; Blood Proteins ; Connectin ; MYOM3 protein, human ; Creatine Kinase (EC 2.7.3.2)
Language English
Publishing date 2015-06-09
Publishing country England
Document type Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID 1108742-0
ISSN 1460-2083 ; 0964-6906
ISSN (online) 1460-2083
ISSN 0964-6906
DOI 10.1093/hmg/ddv214
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Zs.A 3469: Show issues Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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