Researchers used a technique called CRISPR/Cas9-mediated genome editing, which can precisely remove a mutation in DNA, allowing the body’s DNA repair mechanisms to replace it with a normal copy of the gene. The benefit of this over other gene therapy techniques is that it can permanently correct the “defect” in a gene rather than just transiently adding a “functional” one, said Dr. Eric Olson, Director of the Hamon Center for Regenerative Science and Medicine at UT Southwestern and Chairman ofMolecular Biology.
Using CRISPR/Cas9, the Hamon Center team was able to correct the genetic defect in the mouse model of DMD and prevent the development of features of the disease in boys, which causes progressive muscle weakness and degeneration, often along with breathing and heart complications.
“Our findings show that CRISPR/Cas9 can correct the genetic mutation that leads to DMD, at least in mice,” said Dr. Olson, holder of the Pogue Distinguished Chair in Research on Cardiac Birth Defects, the Robert A. Welch Distinguished Chair in Science, and the Annie and Willie Nelson Professorship in Stem Cell Research. “Even in mice with only a subset of corrected cells, we saw widespread and progressive improvement of the condition over time, likely reflecting an advantage of the corrected cells and their contribution to regenerating muscle.”
He also pointed out “this is very important for possible clinical application of this approach in the future. 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.”
Although the genetic cause of DMD has been known for nearly 30 years, there are no treatments that can cure the condition. Duchenne muscular dystrophy breaks down muscle fibers and replaces them with fibrous and/or fatty tissue causing the muscle to gradually weaken.
DMD affects an estimated 1 in 3,600–6,000 male births in the United States, according to the Centers for Disease Control (CDC). Left untreated, those with DMD eventually require use of a wheelchair between age 8 and 11, and have a life expectancy of 25 years. Initial symptoms include difficulty running and jumping, and delays in speech development. DMD can be detected through high levels of a protein called creatine kinase as it leaks into the blood stream, and is confirmed by genetic testing.