A new study of dogs released this week in Science provides a tantalizing glimpse of how life-changing the CRISPR gene editing technology could be for some people in the near future. It suggests that CRISPR may be used to treat an otherwise incurable, deadly genetic disorder known as Duchenne Muscular Dystrophy (DMD).
DMD is the most common form of muscular dystrophy, a generic term for conditions that continually destroy muscle throughout the body. This waste is mainly caused by the inability to use dystrophin, a protein that acts as an adhesive to stabilize muscle fibers.
These conditions are often caused by a genetic defect, and people with DMD have mutations in the gene responsible for dystrophin, which prevents them from doing anything at all.
Since the dystrophin gene is found on the X chromosome, DMD mainly affects boys because girls typically have two X chromosomes and a healthy copy of the dystrophin gene is usually sufficient to prevent serious disease (women may Still Caring and Sustained (1
But as you can see in girls, dystrophin production does not require much dystrophin production to ward off these symptoms, so gene therapy was hoped to significantly improve the lives of those affected, or even complete the disease
The emergence of the CRISPR-Cas system, a relatively cheap and simple gene editing method, has only increased this hope.
There have already been successful studies with mice that used CRISPR to repair DMD mutations to restore some muscle function – also by the team behind this latest study. Her new study is the first to test whether the same can be seen in larger animals.
A few years ago it was discovered that dogs can be born with mutations that led them to develop their own version of DMD ideal test animal. This mutation deletes a specific DNA region on the dystrophin gene that encodes the protein, called exon 50. Without this exon, exon 51 is also out of action, making the production of dystrophin impossible.
Researchers bred four Beagle with DMD, then used CRISPR to manipulate Exon 51 and puzzle it out. These errors, it was theorized, would cause the affected cells to completely skip the exon 51. The expected net result would be a reduced but still functional level of dystrophin production. And that obviously happened.
CRISPR was given to the dogs at the age of one month via a harmless virus that has its place in the heart and muscle tissue. Six to eight weeks later, the researchers found that heart and diaphragm dystrophin levels in the dog receiving the largest dose were 92 percent and 56 percent normal.
It is believed that even 15 percent of normal dystrophin production would be life changing for DMD patients.
"Our strategy differs from other therapeutic approaches to DMD because it restores the mutation that causes the disease and restores normal expression from the repaired dystrophin," said lead author Leonela Amoasii, a researcher at the University's Southwestern Medical Center from Texas, in a statement. "But we still need to do more before we can do it clinically."
On the one hand, the study should only serve as a preliminary demonstration, so the dramatic results should be taken with caution for the time being. The dogs were not observed long enough to know for sure if this recovery would lead to a lasting improvement in symptoms. (They were killed to prevent them from being exposed to possible suffering that could result from their condition and treatment.)
In addition, only about 15 percent of people with DMD have this particular mutation, so other genetic Edits needed to help out the remainder of the approximately 300,000 boys worldwide who are believed to have this disease
And for the praise CRISPR has received, there are real, if sometimes exaggerated, fears that It could lead to unwanted gene mutations that could increase the risk of cancer other health problems. When CRISPR treatments for DMD targeted a person's stem cells, the authors noted in their study that both the positive and the harmful effects could be permanent.
No specific mutations were observed in the dogs outside the target sequence, but it is a risk that other future studies must continue to pay attention to.
Nonetheless, the researchers who founded a company to commercialize their technology have called Exonics Therapeutics to pursue more and longer-term studies that include not only DMD but also other genetic disorders.