For the very first time, scientists survey using gene-editing technology to halt the progression of muscular dystrophy in dogs -- suggesting a possible breakthrough for children with a kind of the disease.
Reporting in the current issue of Science, researchers describe how they used CRISPR technology to edit a naturally happening genetic flaw that causes a version of Duchenne muscular dystrophy in dogs. CRISPR means for a family group of DNA sequences.
The gene correction, in turn, triggered what the scientists call an "unprecedented" improvement in the animals' muscle fibers.
The discovery might hold the key to helping children with Duchenne MD, the most typical kind of muscular dystrophy. MD can be several incurable genetic disorders that cause progressive muscle degeneration.
Duchenne MD primarily affects boys and usually arises in early childhood. Historically, most boys did not survive beyond their teens, but more you live into their 30s these days, according to the Muscular Dystrophy Association.
Duchenne is the effect of a mutation in a gene that makes a critical protein called dystrophin. Without it, muscles throughout the body -- like the heart and diaphragm -- breakdown over time.
"Really the only way to correct this disorder is to have the body to create functional dystrophin," said Eric Olson, business lead researcher on the new research. He's professor and director of University of Texas Southwestern Medical Center's Hamon Middle for Regenerative Science.
To do that, researchers have been learning gene therapy. But with Duchenne MD, Olson stated, there is a hurdle to replacing the defective gene with a functioning one: its size.
"It's way too massive to replace," he explained.
So Olson and his team took a different strategy. They used CRISPR gene-editing technology to fix the gene defect.
The researchers treated four canines that carried the most common mutation seen in people with Duchenne MD -- affecting a location on the dystrophin gene called exon 51. They used a harmless virus to deliver CRISPR components to the exon -- that your technology then "edited."
Within weeks, the researchers reported, the lacking dystrophin protein was restored in muscle through the entire animals' bodies.
The effects were not uniform. In some muscle tissue, dystrophin was created at 3 percent of its regular level. But in the center and diaphragm, the protein was restored to 92 percent and 58 percent of normal, respectively.
The researchers also found proof improved integrity in the animals' muscle fibers.
Olson put the boosts in dystrophin amounts in perspective: There is a medication for Duchenne MD -- called Exondys 51, and approved in the usa in 2016 -- that can be utilized in a minority of sufferers who have a mutation in exon 51.
It has been demonstrated to restore significantly less than 1 percent of dystrophin in skeletal muscle after one year, Olson pointed out.
"Here, we saw really dramatic changes -- beyond what we'd hoped for," he said.
The findings are "very encouraging," said Dr. Sajel Lala Kana, a clinical geneticist at Nicklaus Children's Hospital in Miami.
However they are also very early, she described. "This study displays what happens in these animals for a while," stated Kana, who was not involved in the analysis. "But will this become sustainable over a long period of time?"
Olson agreed that that is clearly a critical question. And there's the issue of if the gene editing could possess unintended adverse effects.
There are two main theoretical safety concerns, according to Olson: "Are there any off-target effects?" he said. "That is, could this accidentally impact the expression of additional genes?"
Another question, Olson said, is if the immune system will respond to the enzyme CRISPR uses to make its gene fixes. Up to now, there have been no signs of that, the researchers said.
While animal studies frequently don't produce the same effects in individuals, Olson said these findings is seen as a promising early stage.
"We're spending so much time on trying to take care of the cause of this disease," he said. "With further study in pets, in a couple of years we may have the ability to move into human trials."
Kana agreed. "There's lots of research going on this field," she stated. "This is how we'll move toward a remedy someday."
In the United States, Duchenne MD impacts one in every 3,500 to 6,000 boys born every year, based on the National Institutes of Health. Often, the company says, there is absolutely no family history of the disease; rather, mutations spontaneously take place in the dystrophin gene.
