Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1

Area of Science:

• Molecular Biology
• Genetics
• Exercise Physiology

Background:

• Myotonic dystrophy type 1 (DM1) is a common adult-onset muscular dystrophy caused by CTG repeat expansion, leading to transcriptomic dysregulation and muscle wasting.
• Strength training offers clinical benefits for DM1 patients, but its molecular effects remain largely uncharacterized.

Purpose of the Study:

• To investigate whether a strength-training program can rescue transcriptomic defects in DM1 patients.
• To correlate molecular changes with clinical improvements in strength.

Main Methods:

• RNA-sequencing (RNA-Seq) was performed on vastus lateralis muscle samples from 9 male DM1 patients before and after a 12-week strength-training program.
• Differential gene expression and alternative splicing analyses were conducted and correlated with one-repetition maximum strength measurements.
• A control group of 6 male individuals did not undergo training.

Main Results:

• While training-induced splicing improvements were generally observed, the specific rescued splicing events varied significantly between individuals.
• Gene expression improvements also showed high inter-individual variability, with the percentage of rescued differentially expressed genes strongly correlating with strength gains.
• Individualized analysis of transcriptome changes revealed training responses not apparent in grouped analyses, likely due to disease heterogeneity and individual responses.

Conclusions:

• Transcriptomic changes are associated with clinical outcomes in DM1 patients undergoing strength training.
• The molecular responses to training are often individual-specific and require personalized assessment for a comprehensive understanding of treatment efficacy.