A research team led by University of Minnesota biochemist James Ervasti, Ph.D., is yielding promising results in the search for a treatment for Duchenne muscular dystrophy, the most common form of muscular dystrophy in children.
Duchenne, which affects only boys (though girls can be carriers), is caused by a genetic mutation preventing the body’s production of dystrophin, a protein crucial to maintaining muscle structure. Without it, muscles stop working and deteriorate. The disease is often fatal by age 20.
Ervasti’s team injected a mouse model with a substitute for the missing dystrophin, repairing the weakening muscle tissue. The substitute is a modified protein called utrophin—a dystrophin relative—with a cell-penetrating tag known as TAT. The team found that, once injected, TAT-utrophin spreads throughout the body efficiently.
This approach overcomes major hurdles in treating this systemic disease because it delivers the therapy to every muscle cell in the body. Also, because every cell makes utrophin naturally, the immune system does not reject the TAT-utrophin therapy.
While not a cure, Ervasti says this treatment could one day be an effective therapy for boys with Duchenne. If the treatment works in studies involving larger animals and humans, researchers hope to develop a drug for boys with Duchenne and start clinical trials within three years.
Ervasti’s team also recently discovered a new function of the missing dystrophin protein that could help scientists develop new therapies.
Previous research had shown that dystrophin protected muscle cells by connecting two of the three filament types responsible for cell shape and durability. Ervasti’s new research shows that dystrophin is also responsible for linking to the third filament type, called microtubules. If a person is missing dystrophin, the microtubules become disorganized, which might contribute to the symptoms of Duchenne.