WASHINGTON — American scientists have for the first time used gene editing technology to halt the progression of Duchenne muscular dystrophy (DMD) in a large mammal, providing a potential lifesaving treatment for the most common fatal genetic disease in children.
The study published on Thursday in the journal Science reported the improvement in the muscle fibers of dogs with DMD, which is caused by a mutation that inhibits the production of dystrophin, a protein critical for muscle function.
Researchers from the University of Texas Southwestern Medical Center used a single-cut gene-editing technique to restore dystrophin in muscle and heart tissue by up to 92 percent of normal levels. The 15-percent threshold is needed to significantly help patients, according to scientists.
DMD, which affects one in 5,000 boys, leads to muscle and heart failure, and premature death by the early 30s. No effective treatment exists, though scientists have known for decades that a defect in the dystrophin gene causes the condition.
“Children with DMD often die either because their heart loses the strength to pump, or their diaphragm becomes too weak to breathe,” said Eric Olson, Director of UT Southwestern’s Hamon Center for Regenerative Science and Medicine. “This encouraging level of dystrophin expression would hopefully prevent that from happening.”
The latest research applied the CRISPR editing technique in four dogs that shared the type of mutation most commonly seen in DMD patients.
Scientists used a harmless virus called adeno-associated virus (AAV) to deliver CRISPR gene-editing components to exon 51, one of the 79 exons that comprise the dystrophin gene.
According to the study, CRISPR edited the exon, and within several weeks the missing protein was restored in muscle tissue throughout the body, including 92-percent correction in the heart and 58 percent in the diaphragm, the main muscle needed for breathing.
“Our strategy is different from other therapeutic approaches for DMD because it edits the mutation that causes the disease and restores normal expression of the repaired dystrophin,” said Leonela Amoasii, lead author of the study who worked at Olson’s lab.
The lab will next conduct longer-term studies to measure whether the dystrophin levels remain stable and to ensure the gene edits do not have adverse side effects before entering a clinical trial.