While myostatin blocks muscle differentiation and growth, inflammation contributes to muscle death in neuromuscular diseases. In muscular dystrophy, the immune process is heightened, which contributes to chronic inflammation that kills muscle cells. The protein nuclear factor kappa B (NF-kB) is implicated in this process, suggesting that blocking the protein should stop the inflammation. But to date, anti-inflammatory medications used to treat DMD do not appear to be effective in slowing progression of the disease.
A Muscle Group study appearing in the Journal of Clinical Investigation confirmed that NF-kB is responsible for the chronic inflammation and muscle-cell death that are hallmarks of DMD. Also that activation of the protein is required to block the ability of skeletal muscle cells to regenerate the cells destroyed by that very same inflammation.
“This dual role makes the protein particularly attractive as a target for therapy,” said Dr. Guttridge. “NF-kB is driving the inflammation – but that’s only half of the story. It also plays a role in skeletal muscle cells by blocking their ability to regenerate.”
The group found that inhibiting the protein reduced inflammation and allowed muscle tissue to regenerate in animals with a disease similar to muscular dystrophy, suggesting that a drug against NF-kB could one day serve as therapy to prevent progression of the disease in humans. “Any drug developed to block NF-kB might slow the degeneration-regeneration cycles in DMD patients or might even reduce the initial inflammation, which would delay onset of that cyclical process,” said Dr. Guttridge.