As originally discussed in Muscular Dystrophy News Today, a recent study has discovered that increasing levels of utrophin in the body can improve muscle strength, form, and function for patients with Duchenne muscular dystrophy. This is a huge step forward in the journey to improve patient care. Learn more about the findings in the research article published in Scientific Reports.
About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a type of muscular dystrophy caused by an inability to make dystrophin in the body. Dystrophin, a protein, helps strengthen muscles and protect them from damage. As a result of low dystrophin levels, people with DMD experience muscle weakness, heart and respiratory weakness, and quadriplegia.
Patients with DMD normally begin showing symptoms in early childhood. These include difficulty with motor skills, fatigue, and progressive muscle weakness. This disorder is caused by a genetic mutation. Want to know more about DMD? Take a look at our website.
The Findings
Researchers wanted to understand if there was any way to address muscle weakness and degeneration caused by DMD without resorting to gene therapy. Admittedly, gene therapy can be effective in creating targeted treatment options. However, in this case, researchers felt that it might be better for patients to address their needs on a biological level. Also, previous attempts to raise protein levels through activating genetic sequences failed as normal bodily functions stepped up to keep this from happening.
Researchers focused on two proteins: dystrophin and utrophin. As stated earlier, dystrophin helps create muscle strength within the body. But because the dystrophin gene is so large, patients with DMD cannot just be given extra dystrophin. Instead, dystrophin treatments would require cellular delivery via adeno-associated viruses.
So What’s the Issue?
Patients with Duchenne muscular dystrophy don’t really produce any dystrophin. So even by introducing it via cellular delivery, the body’s immune system may not recognize the dystrophin. Instead of accepting it, the body might attack it as a foreign invader. If it is under attack by the immune system, the treatment is rendered ineffective.
Utrophin to Treat Duchenne Muscular Dystrophy
Utrophin is another protein in the body that is usually produced during embryonic development. It is similar to dystrophin, and researches believed that increasing utrophin levels in patients with DMD may help increase muscle function. Because the body already produces utrophin, introducing additional utrophin does not set off alarm bells like introducing dystrophin would.
However, utrophin is not produced as much in adulthood. So researchers wanted to determine if they could use any small molecules to help spur this production. They identified 27 molecules out of a database of over 3,000. Next, they tested the 10 most promising molecules.
Within 24 hours, 80% of the molecules had increased protein levels in muscle cells. However, Trichostatin A (TSA) proved to be the most helpful. TSA raised utrophin by 3.9x.
Using mouse models of Duchenne muscular dystrophy, researchers studied the impact of 3 months worth of TSA injections. They found that mice given TSA had double the amount of utrophin as well as heightened muscle function compared to mice given a control shot.
There is still more research to be done to understand the impact of TSA and utrophin on human patients with Duchenne muscular dystrophy. However, the research so far is promising and suggests that patients may even be able to recover some muscle function later in life. Researchers hope to hold clinical trials soon.
