Serum proteomic profiling reveals fragments of MYOM3 as potential biomarkers for monitoring the outcome of therapeutic interventions in muscular dystrophies

Hum Mol Genet. 2015 Sep 1;24(17):4916-32. doi: 10.1093/hmg/ddv214. Epub 2015 Jun 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Biomarkers
  • Blood Proteins
  • Connectin
  • MYOM3 protein, human
  • Creatine Kinase