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Research Connects DM and Duchenne Muscular Dystrophy

Findings Point to Potential for New Therapy Research

Since the discovery of the mutation causing type 1 myotonic dystrophy (DM1) was discovered in 1992, researchers around the world have been trying to understand how the DNA mutation causes such a wide variety of symptoms. Studies on fish and mice now show a link between the DMD splicing change which likely contributes to the kinds of muscle deterioration experienced by many people with DM1.

One of the main effects of the mutation is improper processing of RNA molecules in the cell, known as splicing changes. While hundreds of splicing changes are known to occur in DM, only a few have been directly connected to symptoms such as myotonia, insulin resistance, and muscle weakness. Many of the splicing changes have still not been connected with any symptoms, and many symptoms still remain unexplained.

One known splicing change in DM1 is in a gene called DMD. Interestingly, mutations in the DMD gene cause Duchenne and Becker muscular dystrophy. Even though the mutations causing these two conditions are not found in people with DM1, the conditions are similar to DM1 in their progressive weakness and deterioration of muscle.

Given the commonality in some symptoms and changes that can occur in the same gene, researchers from the Sorbonne University in Paris, led by Dr. Denis Furling, investigated whether the DMD splicing change seen in people with DM1 could be causing muscle symptoms. The researchers confirmed that the splicing change leads to the creation of a longer DMD protein. The longer form of DMD is known as an embryonic or fetal form because it should only be found in developing fetuses during pregnancy, and not adults. Their computer modeling of the protein suggests the embryonic DMD protein will alter its structure and function.

To test whether this switch to the embryonic form of DMD truly has any consequences in animals, they created a drug that would force the embryonic form to be present throughout the life of a zebrafish. As expected, they observed large structural changes in the shape of the developing fish, and impaired mobility. The researchers then did a similar experiment in mice. They found that mice with the embryonic form of DMD were less able to protect their muscle from injury, and had reduced strength.

The results from these experiments support a link between the DMD splicing change and muscle abnormalities. Overall, the researchers conclude that the DMD splicing change likely contributes to the progressive muscle deterioration seen in many people with DM1.

This study, along with others that find links between symptoms and splicing changes, may have important implications because therapies could be developed to reverse specific splicing changes. More research is necessary to highlight important splicing changes in DM1 and determine whether reversing them would be beneficial as a future therapeutic approach.






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