Serum proteomic profiling reveals fragments of MYOM3 as potential biomarkers for monitoring the outcome of therapeutic interventions in muscular dystrophies.
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| 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.
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| Authors | Jérémy Rouillon, Jérôme Poupiot, Aleksandar Zocevic, Fatima Amor, Thibaut Léger, Camille Garcia, Jean-Michel Camadro, Brenda Wong, Robin Pinilla, Jérémie Cosette, Anna M L Coenen-Stass, Graham Mcclorey, Thomas C Roberts, Matthew J A Wood, Laurent Servais, Bjarne Udd, Thomas Voit, Isabelle Richard, Fedor Svinartchouk |
| Journal | Human molecular genetics (Hum Mol Genet) Vol. 24 Issue 17 Pg. 4916-32 (Sep 01 2015) ISSN: 1460-2083 [Electronic] England |
| PMID | 26060189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © The Author 2015. Published by Oxford University Press. |
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