Researchers at the University of Texas (UT) Southwestern Medical Center have developed a technique that corrects a mutation leading to Duchenne muscular dystrophy (DMD). The technique, called CRISPR/Cas9-mediated genome editing, removes the mutation entirely in mice, and could have far-reaching consequences in the treatment of muscular dystrophy in people.

According to the Centers for Disease Control, DMD appears in approximately one out of every 3,500 male births in the US (but rarely appears in girls). It usually strikes before the age of six, often confining patients to a wheelchair before adolescence, with death generally before age 25.

It is a severe form of muscular dystrophy caused by a mutation in a gene called dystrophin that leads to loss of function and strength, not only in voluntary muscles such as those in the arms and legs, but also (later) in the cardiovascular system. It has no cure and existing treatments focus on improving quality of life more so than on halting the progression of the disease.

Using CRISPR/Cas9-mediated genome editing to precisely remove the mutation in DNA responsible for DMD, the UT team found that the mouse's DNA repair mechanisms replace it with a normal copy of the gene. Unlike other approaches, such as exon skipping (causing cells to "skip" the mutation) and gene therapy (which delivers functional dystrophin via a harmless virus but retains the original dysfunctional copy of the gene), this new technique could potentially correct the problem at the source. In other words, it could permanently fix genetic defects, thereby promising completely functional DNA protein. This, in turn, could have a big impact on muscle regeneration over time.

"At the moment, we still need to overcome technical challenges, in particular to find better ways to deliver CRISPR/Cas9 to the target tissue and to scale up," says Dr. Eric Olson, director of the Hamon Center for Regenerative Science and Medicine at UT Southwestern. "But in the future we might be able to use this technique therapeutically, for example to directly target and correct the mutation in muscle stem cells and muscle fibers."

Mice injected with even just a subset of corrected cells showed progressive, widespread improvement over time, the research found. The hope is that the technique can one day be adapted for human treatment of muscular dystrophy.

"This is very important for possible clinical application of this approach in the future," Dr. Olson explains. "Skeletal muscle is the largest tissue in the human body and current gene therapy methods are only able to affect a portion of the muscle. If the corrected tissue can replace the diseased muscle, patients may get greater clinical benefit."

The research is described in a paper published in the journal Science.