A research team from UT Southwestern Medical Center suggests that the use of a gene-editing technique helped stop the progression of Duchenne muscular dystrophy (DMD) in young mice.
A media release from UT Southwestern Medical Center explains that 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, according to the Centers for Disease Control and Prevention and other estimates, and often leads to premature death by the early 30s.
The technique used by the UT Southwestern researchers—called CRISPR/Cas9-mediated genome editing—helped permanently correct the DMD mutation that causes the disease in young mice, per the release.
The study was published recently in Science.
“This is different from other therapeutic approaches, because it eliminates the cause of the disease,” said the study’s senior author Eric Olson, PhD, Chairman of Molecular Biology, and Co-Director of the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center at UT Southwestern, in the release.
Olson’s team first used this technique in 2014 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. It also raised several challenges for clinical applications of gene editing. Since germ line editing is not feasible in humans, strategies would need to be developed to deliver gene-editing components to postnatal tissues, the release explains.
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 release continues.
The CRISPR genome-editing technology, which was developed by a researcher at University of California at Berkeley, was picked as the “Breakthrough of the Year” scientific development by Science, the release notes.
“Importantly, in principle, the same strategy can be applied to numerous types of mutations within the human DMD patients,” adds Olson, who also serves as director of the Hamon Center for Regenerative Science and Medicine, and holds the Annie and Willie Nelson Professorship in Stem Cell Research, the Pogue Distinguished Chair in Research on Cardiac Birth Defects, and the Robert A. Welch Distinguished Chair in Science, in the release.
The research team is working to apply this gene-editing technique to cells from DMD patients and in larger preclinical animal models, per the release.
[Source(s): UT Southwestern Medical Center, EurekAlert]