Duchenne muscular dystrophy is a genetic disorder currently without a cure. It causes progressive muscle degeneration and weakness. Duchenne Muscular Dystrophy, or DMD, is characterized by an absence of dystrophin. Dystrophin is a protein that keeps muscles intact, which when absent lead to a loss of muscle function and strength. This lack of dystrophin begins in early childhood between ages three and five mostly in males with 1 in 5,000 males inflicted and a rare
occurrence in females. By later ages, individuals are forced into wheelchairs and put on respirators as their diaphragms weaken until an early death usually in their 20’s or early 30’s due to heart failure or an inability to breath.
Despite not having a cure for Duchenne Muscular Dystrophy, scientists are performing the first trials in large mammals, dogs. Many dog breeds can also be inflicted by the lack of dystrophin and thus have Duchenne Muscular Dystrophy. Four of these inflicted dogs have been chosen at only one-month-old to be treated using a harmless virus called adeno-associated virus or AAV. This harmless virus is delivering the CRISPR Cas9 protein gene-editing components to make a single strategic cut in faulty DNA to “exon 51, one of the 79 exons that comprise the dystrophin gene.”
These dogs were tracked and within several weeks of the CRISPR editing the missing protein was reported in muscle tissue throughout the body with as much as 92% correction in the heart and 58% correction within the diaphragm, which is the main muscle needed for breathing. While there is a clear success in the current trials with improvements greater than 15%, they are still far from human clinical trials as the question still remains if the stable levels of dystrophin do not have adverse side effects. The corrections made using CRISPR was previously noted in having successfully corrected mice and human cells only increasing the hope provided by these trials. The trial is already being called “promising” and might one day be considered “groundbreaking.”
Not only providing hope for those with DMD, but these trials also provide a significant step towards single gene editing to treat an incurable disease. While larger studies are still to be conducted, the individuals working on this study at the Royal Veterinary College in London and UT Southwestern Medical Center in the United States are eager for the study to grow. One such leader in this study, Dr.Olson from UT Southwestern has even gone as far as spawning a biotechnological company called Exonics Therapeutics Inc. with the hope of further optimizing this technology for the clinic on top of his role at the University.