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Journal of Neuromuscular Diseases
Journal of Neuromuscular Diseases
Volume 11, issue 5

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Roussel, Marie-Pier | Ravel-Chapuis, Aymeric | Gobin, Jonathan | Jasmin, Bernard J. | Leduc-Gaudet, Jean-Philippe | Gagnon, Cynthia | Duchesne, Elise

Background: Myotonic dystrophy type 1 (DM1) is a slowly progressive disease caused by abnormal CTG repetitions on the dystrophia myotonica protein kinase (DMPK ) gene. Long mRNA from CTG repetitions stabilizes in nuclear foci and sequester muscleblind-like splicing regulator 1 (MBNL1). Cardinal signs of DM1 include muscle wasting and weakness. The impacts of DM1 progression on skeletal muscle are under-researched.

Objective: Identifying physiopathological markers related to maximal strength loss over time in DM1.

Methods: Twenty-two individuals with DM1 participated in two maximal isometric muscle strength (MIMS) evaluations of their knee extensors and two vastus lateralis muscle biopsies, 3 years apart. Muscle fiber typing, size (including minimal Feret’s diameter [MFD] and atrophy/hypertrophy factors [AF/HF]), and nuclear foci and MBNL1 colocalization (foci/MBNL1+) were evaluated. Immunoblotting was used to measure glycogen synthase kinase-3 beta (GSK3Beta ), p62, LC3BI, LC3BII, and oxidative phosphorylation proteins.

Results: There are significant correlations between the fold changes of MIMS with type 1 fiber MFD (p=0.483) and AF (p=–0.514). Regression analysis shows that baseline percentage of foci/MBNL1+ nuclei and strength training explain 44.1% of foci/MBNL1+ nuclei percentage variation over time. There are fair to excellent correlations between the fold changes of MIMS and GSK3? (p=0.327), p62 (p=0.473), LC3BI (p=0.518), LC3BII (p=–0.391) and LC3BII/LC3BI (p=–0.773).

Conclusion: Type 1 MFD decrease and AF increase are correlated with MIMS loss. There seems to be a plateau effect in foci/MBNL1+ nuclei accumulation and strength training helps decrease this accumulation. Autophagy marker LC3BII/LC3BI ratio has a good biomarker potential of MIMS loss, but more investigations are needed.