Gene-Editing Technique Successfully Stops Progression of Duchenne Muscular Dystrophy

Members of the UT Southwestern team whose research successfully halted progression of a form of muscular dystrophy in mice included (l-r) Dr. Chengzu Long, Dr. Eric Olson, Dr. Rhonda Bassel-Duby, Dr. Leonela Amoasii, John Shelton, and Alex Mireault. Credit: UT Southwestern Medical Center

Using a new gene-editing technique, UT Southwestern Medical Center scientists stopped progression of Duchenne muscular dystrophy (DMD) in young mice. If efficiently and safely scaled up in DMD patients, this technique could lead to one of the first successful genome editing Rx’s.

DMD, the most common and severe form of muscular dystrophy among boys, is characterized by progressive muscle degeneration and weakness. It is caused by mutations in the X-linked DMD gene that encodes the protein dystrophin. The disease affects one in 3,500 to 5,000 boys, and often leads to premature death by the early 30s. Although the genetic cause of DMD has been known for nearly 30 years, no effective treatments exist. The disease breaks down muscle fibers and replaces them with fibrous or fatty tissue, causing the muscle to gradually weaken. This condition often results in heart muscle disease, or cardiomyopathy, the leading cause of death in these patients.

In 2014, Dr. Olson’s team first used this technique – called CRISPR/Cas9-mediated genome editing – to correct the mutation in the germ line of mice and prevent muscular dystrophy. This paved the way for novel genome editing-based therapeutics in DMD. But as germ line editing is not feasible in humans, strategies would need to be developed to deliver gene-editing components to postnatal tissues. To test this out, researchers delivered gene-editing components to the mice via adeno-associated virus 9 (AAV9). DMD mice treated with this technique produced dystrophin protein and progressively showed improved structure and function of skeletal muscle and heart. “The CRISPR/Cas9 system is an adaptive immune system of single-celled organisms against invading virus. Ironically, this system was hijacked, we packaged it into a nonpathogenic virus, and corrected a genetic mutation in an animal model,” added Dr. Long.

“Importantly, in principle, the same strategy can be applied to numerous types of mutations within the human DMD patients,” added Dr. Olson.
Now, the team is working to apply this gene-editing to cells from DMD patients and in larger preclinical animal models.
http://www.utsouthwestern.edu/newsroom/news-releases/year-2015/dec/duchenne-muscular-dystrophy-olson.html