Exercise Improves Muscle Function In Myotonic Dystrophy Type 1 Patients Independent Of Changes In Pathophysiology
Bibliographic record
Abstract
Myotonic dystrophy type 1 (DM1) is the leading life-limiting muscular dystrophy in adults. DM1 present with accelerated muscle atrophy, myotonia, cardiac arrhythmias and respiratory dysfunction. Primary hypothesis for DM1 manifestation is the abnormal localization and expression of several RNA binding proteins due to a ‘CTG’ DNA repeat expansion in the Dystrophia Myotonic Protein Kinase (DMPK) gene. Notably, the DM1 mutation results in the loss- and toxic gain of function mechanism in the muscleblind-like protein family (MBNL) and CUG-binding protein 1, respectively. Aerobic exercise has been deemed safe in DM1 patients, however, its efficacy on muscle function and DM1 pathophysiology in patients has yet to be elucidated. PURPOSE: To examine the benefits of 12-weeks of cycle ergometry on muscle function and cellular mechanisms in DM1 patients. METHODS: 11 DM1 patients (DM1, 42.6 ± 3 y) were recruited from the Neuromuscular Clinic at McMaster University Medical Centre along with age matched to healthy controls (CON, 42.5 ± 2 y). DM1 and CON performed VO2max testing, muscle functional tests and muscle biopsy from the vastus lateralis. Following the intervention (3x/wk @ ~65% VO2max), DM1 completed post testing. RESULTS: Cycle ergometry improved cardiorespiratory fitness by ~30% in DM1 (p < 0.05). Additionally, total lean mass and fiber area were increased following exercise (p < 0.05). Increases in muscle mass translated to improvements in physical function as measured by 6-min walk test, 5x sit to stand test, and timed up-and-go test (p < 0.05). Mitochondrial respiration and protein content were lower in DM1 relative to CON but were augmented following exercise (p < 0.05). Subcellular fractionation of revealed an increase in cytosolic content of MBNL2 while in situ fluorescence hybridization revealed no changes in MBNL1 sequestration in response to exercise in DM1 as measured by MBNL1/CUG)n positive myonuclei (p > 0.05). However, there was a reduction in the in average number of foci within myonuclei (p = 0.06) CONCLUSION: Exercise is a low-cost effective intervention to mitigate muscle atrophy in DM1 patients. Furthermore, training can augment mitochondrial function preventing muscle loss. Lastly, exercise benefits in DM1 patients appear to occur independent of changes in DM1 pathophysiology.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".