Towards the Identification of Biomarkers for Muscle Function Improvement in Myotonic Dystrophy Type 1

Abstract

Background: Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. In DM1 patients, skeletal muscle is severely impaired, even atrophied and patients experience a progressive decrease in maximum strength. Strength training for these individuals can improve their muscle function and mass, however, the biological processes involved in these improvements remain unknown. Objective: This exploratory study aims at identifying the proteomic biomarkers and variables associated with the muscle proteome changes induced by training in DM1 individuals. Methods: An ion library was developed from liquid chromatography-tandem mass spectrometry proteomic analyses of Vastus Lateralis muscle biopsies collected in 11 individuals with DM1 pre-and post-training. Results: The proteomic analysis showed that the levels of 44 proteins were significantly modulated. A literature review (PubMed, UniProt, PANTHER, REACTOME) classified these proteins into biological sub-classes linked to training-induced response, including immunity, energy metabolism, apoptosis, insulin signaling, myogenesis and muscle contraction. Linear models identified key variables explaining the proteome modulation, including atrophy and hypertrophy factors. Finally, six proteins of interest involved in myogenesis, muscle contraction and insulin signaling were identified: calpain-3 (CAN3; Muscle development, positive regulation of satellite cell activation), 14-3-3 protein epsilon (1433E; Insulin/Insulin-like growth factor, PI3K/Akt signaling), myosin-binding protein H (MYBPH; Regulation of striated muscle contraction), four and a half LIM domains protein 3 (FHL3; Muscle organ development), filamin-C (FLNC; Muscle fiber development) and Cysteine and glycine-rich protein 3 (CSRP3). Conclusion: These findings may lead to the identification for DM1 individuals of novel muscle biomarkers for clinical improvement induced by rehabilitation, which could eventually be used in combination with a targeted pharmaceutical approach to improving muscle function, but further studies are needed to confirm those results.