A baby boy born with Duchenne muscular dystrophy looks perfectly healthy, until he develops coordination problems sometime around age 2 or 3. It’s often then that families learn their child has this tragic disease.
Duchenne, which affects only boys (girls may 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, the most common form of muscular dystrophy in children, is often fatal by age 20.
To expedite the development of promising treatments for Duchenne, the Muscular Dystrophy Association, Nash Avery Foundation, Charley’s Fund, and the Foundation to Eradicate Duchenne are funding University of Minnesota research that is yielding promising new results.
That includes research led by biochemist James Ervasti, Ph.D., whose team showed last spring that it is possible to replace dystrophin in mice that have muscular dystrophy. The team injected a mouse model with a substitute for the missing dystrophin, repairing weakening muscle tissue. The substitute is a modified protein called utrophin—a dystrophin relative—with a cell-penetrating tag known as TAT.
The therapy is promising because it bypasses the major hurdles encountered in other potential new treatments, such as gene and stem cell therapies. Those barriers include difficulty delivering treatment to every muscle cell in the body and immune system rejection.
Once injected, TAT-utrophin spreads throughout the body and penetrates the muscle cell wall to substitute for the missing dystrophin. Because every cell in the body makes utrophin naturally, TAT-utrophin avoids the immunity issues.
Although it’s not a cure, the treatment could be an effective therapy for boys with Duchenne. Ervasti is hopeful that human clinical trials can start within three years.
In addition to this development, Ervasti’s team also discovered a new function of the missing dystrophin protein that could help in developing additional new therapies.
Previous research had shown that dystrophin protected muscle cells by connecting two of the three filaments types responsible for cell shape and durability. Ervasti’s new study, published in the August 3, 2009, online edition of the Journal of Cell Biology, shows that dystrophin is also responsible for linking to the third filament type, called microtubules, which form a highly ordered lattice in the muscle. Without dystrophin, the microtubules become disorganized.
These recent discoveries open the possibility of replacing defective dystrophin and the development of therapies to extend the lives of boys born with Duchenne muscular dystrophy.
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