For the first time ever, researchers have used CRISPR genetic editing to stop the progression of Duchenne muscular dystrophy (DMD) in a large mammal -- a dog. The results of the study now give thousands of children hope around the world.
A team from UT Southwestern's Hamon Center for Regenerative Science and Medicine created the genetic technique that could offer a solution to DMD. Researchers used a single-cut gene-editing technique to restore dystrophin in muscle to up to 92 percent of its normal levels. Previous studies suggest only a 15 percent threshold can help patients.
Muscular dystrophies are diseases stemming from a genetic defect. In time, this leads to muscular weakness, a decrease in mobility, and daily tasks become difficult. DMD affects one in every 3,500 people aged 5 - 24 years old. Males are significantly more likely to be affected; while girls can also have the genetic marker for DMD, males will show symptoms of DMD sooner and be more affected. What makes DMD particularly harmful is that it starts muscle weakness in children before they even reach 5 years old.
“Children with DMD often die either because their heart loses the strength to pump, or their diaphragm becomes too weak to breathe,” said Dr. 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.”
Not only does DMD lead to muscular failure, but it also leads to heart failure in young people. The average age of death for someone with DMD is their early 30s.
The UT Southwestern group published their research in a recent issue of the journal Science. They establish a proof-of-concept for a single-cut editing in dystrophic muscle that could put them on a quick path to clinical trials.
Their latest research used that proof-of-concept technique on dogs -- the largest mammal to undergo this type of treatment. They used four dogs that shared the type of genetic mutation most often found in DMD patients. The researchers then used a harmless virus called an adeno-associated virus (AAV) to deliver the genetically modified components to the dystrophin gene.
Within weeks, the missing protein was restored in all four canines. There was also a 92 percent correction in the heart and 58 percent in the dogs' diaphragms.
“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 Dr. Leonela Amoasii, lead author of the study and Assistant Instructor of Molecular Biology in Dr. Olson’s lab. “But we have more to do before we can use this clinically.”
The results, while promising, aren't quite ready for human trials just yet. The next step for the lab includes conducting longer-term studies to make sure the dystrophin levels stay stable. The researchers also want to ensure there are no adverse side effects to the gene editing.
UT Southwestern's gene therapy center could see clinical trials of this DMD solution within the next several years if all goes according to plan, Dr. Olson noted.
The research is published in the journal Science.