Duchenne Muscular Dystrophy is the most common and severe childhood form of muscular dystrophy (MD), affecting one in 3,500 boys. The disease progressively weakens muscles cells and tissues until muscle degradation is so severe that the patient dies, most often in their late teens or twenties. Scientists at Brown University in Providence, Rhode Island and the University of Pennsylvania, hope their research into the human protein, biglycan, will ultimately improve the condition of muscular dystrophy sufferers. Their studies have shown that biglycan significantly slows muscle damage and improves function in mice with the Duchenne genetic mutation. Human clinical trials will be the next step.
Boys with the genetic mutation causing Duchenne MD (as the gene is on the X chromosome MD mostly affects males; female carriers have milder symptoms) are unable to produce dystrophin, a protein that keeps muscles strong.
Dystrophin is part of a complex protein that connects the cytoskeleton of a muscle fiber to the tissue framework surrounding each cell through the cell membrane. In cases of muscular dystrophy, contraction of the muscle leads to disruption of the outer membrane of the muscle cells and eventual weakening and wasting of the muscle.
The research, published online on 27 December in Proceedings of the National Academy of Sciences, found that biglycan delivered to the bloodstream restores the muscle-strengthening presence of another protein called utrophin. Utrophin is prevalent in very young children and although it still exists to a far lesser degree in adults, it is not available in a way that can benefit those with muscular dystrophy.
The muscle-strengthening effect of biglycan continued through the testing and there were no indications of side effects on kidney or liver function.
In one experiment there was a 50-percent reduction in “centrally nucleated” fibers in the muscle tissue of mice treated with biglycan treated compared to untreated mice. Biologists recognize the fibers as indicators of recent tissue damage and repair, so a reduction suggests that the muscle tissue is suffering less damage.
In addition, a standardized stress test simultaneously stretched and contracted mouse muscle. Eventually even healthy muscle is weakened however the muscles of muscular dystrophy mice treated with biglycan lost their strength 50 percent more slowly in some muscles than in untreated mice.
“This is all aimed at getting a therapy that will meaningfully improve the condition of patients,” said Justin Fallon, professor of neuroscience at Brown University and the senior author of the Paper.