Progressive muscle disorder in mice can be corrected by genetic therapy

May 25, 2023 | Histopathology

Recently, a research team from the Massachusetts General Hospital utilized targeted drugs in restoring muscle strength and correcting myotonia in mice with myotonic dystrophy. These could lead to new treatment approaches for affected patients.

In myotonia, abnormal processing or splicing of the transcript leads to a truncated or poorly functioning Clcn1, which is a protein that regulates the flow of chloride ions into muscle cells. Moreover, the degree of weakness in patients experiencing myotonic dystrophy is linked with increased amounts of oxidative, rather than glycolytic, muscle fibers. These fibers vary in how they acquire energy for contraction.

Correcting the abnormal splicing in mice having myotonic dystrophy was done through genetic therapy that included antisense oligonucleotides (ASOs). Based on a code that aims at correcting abnormal splicing of Clcn1, it boosts the number of functional Clcn1 when injected directly into an animal's muscles. Muscle health is restored with the increased amounts of glycolytic muscle fibers.

This research study was able to show that muscle fiber type transitions in myotonic dystrophy resulting from myotonia are not irreversible. Clcn1-targeting therapies can be a way to reduce muscle injury in patients.