Protein Could Aid Muscle Repair In Muscular Dystrophies, According to Study

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Dilated Cardiomyopathy and DMD

A new study entitled “GRAF1 deficiency blunts sarcolemmal injury repair and exacerbates cardiac and skeletal muscle pathology in dystrophin-deficient mice” and published in the Skeletal Muscle Journal by Chapel Hill, North Carolina and Northwestern University in Chicago researchers, demonstrates that the GRAF1 protein aids in the repair of acute muscle injury. A lack of GRAF1 might contribute to muscle degeneration in people with muscular dystrophy (MD).

MDs are a category of progressive muscle diseases caused by specific genetic mutations. There are several different types of MDs, which over time, cause muscle degeneration and weakness, greatly impairing mobility and quality of life and in some cases leading to patients’ death.

The current study was led by Kaitlin C. Lenhart of the Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, who along with her collaborators, induced injury in mice muscles using a laser, evaluating whether GFAP1 was necessary for muscle repair. The investigators also studied mice that were genetically modified to lack GRAF1 and compared their muscles to those of normal mice. They analyzed the extent of injury to both the heart and skeletal muscles of the animals.

Using a specialized dye to track GRAF1, researchers found that the protein increases in muscles following injury, indicating it may help in muscle repair. They also found that mice lacking GRAF1 had degenerated muscles compared to mice with normal levels of GRAF1. Muscle degeneration was even more severe if mice also lacked dystrophin–a protein that is depleted in Duchenne muscular dystrophy (DMD), responsible for the muscle weakness observed in this disease.

Muscle degeneration appeared identical to the damage observed in mice lacking both dystrophin and the protein dysferlin, as such, the team wanted to determine whether GRAF1 regulates dysferlin. Upon further experiments researchers observed that “consistent with a model that GRAF1 facilitates dysferlin-dependent membrane patching, we found that GRAF1 associates with and regulates plasma membrane deposition of dysferlin.” It therefore appears that dysferlin requires GRAF1 in order to act on muscles.

In their report, the authors note that “Overall, our work indicates that GRAF1 facilitates dysferlin-dependent membrane repair following acute muscle injury. These findings indicate that GRAF1 might play a role in the phenotypic variation and pathological progression of cardiac and skeletal muscle degeneration in muscular dystrophy patients.”

Based on these results it appears that GRAF1 is an important protein to help maintain muscle cells, acting alongside the protein dysferlin. Future research on medications or strategies that specifically act to increase GRAF1 may aid in the development of new treatments for MD. However, future studies on the function of GRAF1 in humans and in MD is necessary.