The science of gene editing has progressed rapidly in the last decade alone, and researchers have already made a few potentially life changing—and perhaps life saving—breakthroughs. One such advance is that scientists used gene editing to halt the progression of muscular dystrophy in dogs, and it could help humans suffering with the genetic disorder Duchenne muscular dystrophy in the future, Laurel Hamers at ScienceNews reports this week, .
Duchenne muscular dystrophy (DMD) is one of nine types of muscular dystrophy, which progressively leads to muscle wasting and weakness. In DMD, a genetic mutation prevents the body from producing protein called dystrophin, which helps protect muscles from damage and work properly. In some cases, however, low levels of the protein weaken the skeletal and heart muscles causing heart to pump improperly—eventually leading to death. It’s believed 300,000 people worldwide suffer from the disease.
According to Megan Molteni at Wired, researcher Eric Olson at the University of Texas Southwestern Medical Center had previously worked with CRISPR technology to correct dystrophin mutations in mice and human heart cells. For the new study published in the journal Science, he decided to try the technique on a line of dogs whose male descendents often develop the canine version of the disease. Olson had previously discovered that a segment of DNA called an exon, specifically on exon 51—which is one of the 79 exons that make up the dystrophin gene—was a hot spot for mutations that caused DMD.
The experiment included four beagles that had the DMD mutation. CRISPR, in essence, is a way to hunt down and cut a strand of genetic code using an enzyme, disabling or altering the gene. In this case, the researchers used a virus, called adeno-associated virus, to carry the editing tools to exon 51, injecting two of the four dogs with the compound in the lower legs and infusing the other two intravenously.
Over the course of eight weeks, the gene editor did its job, altering exon 51. It’s thought that a restoration of 15 percent of the dystrophin protein in muscles would be enough to relieve DMD. According to a press release, the technique went well beyond that in some muscles, restoring 92 percent of the expected dystrophin protein to the dogs’ hearts and 58 percent to their diaphragm. All of the muscles examined showed improvements, except the tongue, which only had only 5 percent of normal levels.
“We’re certainly in that ballpark with these dogs,” Olson tells Wired’s Molteni.“They showed obvious signs of behavioral improvement—running, jumping—it was quite dramatic.”
The study is promising, but the researchers say they need to conduct longer term studies to see if dystrophin levels remain elevated and to make sure there are no side effects before they begin to think about trying the technique on humans.
“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,” Leonela Amoasii, a member of Olson's lab and lead author of the study says in the release. “But we have more to do before we can use this clinically.”
Moving cautiously is a must. Back in 1999, during the beginnings of gene therapy, the death of a patient during a clinical trial put the brakes on the field for years. So researchers are careful to move forward slowly. Still, the field holds enormous promise, not just for DMD but for a host of genetic diseases. “This work represents a small, but very significant step towards the use of gene editing for DMD,” geneticist Darren Griffin at University of Kent tells Alex Therrien at the BBC. “Any steps towards significant treatment regimes can only be good news. In the fullness of time, this paper may well be seen as one of the ground-breaking studies that led the way to effective treatment.”
In the meantime, the very good doggos from this study are certainly grateful.