Scientists successfully use ‘controversial’ gene editing technique to correct muscle disorder

Scientists successfully used the gene editing technique called Clustered regularly-interspaced short palindromic repeats (CRISPR) to treat a debilitating genetic muscle disorder. A new study shows the preliminary evidence that CRISPR could be an effective treatment to restore muscle function in patients with the disorder, called Duchenne muscular dystrophy (DMD), that could severely weaken muscles and cause death.

Researchers from Duke University used the technique to treat an adult mouse model suffering from DMD, a debilitating genetic disease occurring in one in 3,500 males. DMD can cause muscle degeneration, loss of mobility, and in some cases premature death.

The study, published in the journal Science, shows CRISPR has improved the muscles of the mouse that are responsible for cardiac and pulmonary health. Before the tests, these muscles were severely weakened by DMD.

People develop DMD due to problems with the body's ability to produce dystrophin, a long protein chain connecting the interior of a muscle fibre to a surrounding support structure. Dystrophin is composed of a gene, called exons, which could be affected by a debilitating mutation that can stop dystrophin to be created.

Without the support of dystrophin, muscles would shred and slowly deteriorate, leading the patient to be wheelchair-bound by age 10 and don't live beyond their 20s or early 30s, researchers said. DMD commonly affects newborn males.

Despite the effectiveness of CRISPR, many geneticists reportedly have raised concerns over the proper use of the technique as it may potentially alter the environment. However, Duke researchers said their study shows the potential of the gene editing technique to correct some genetic disorders post-birth.

The results also indicate it is the first time CRISPR has successfully treated a genetic disease in a fully developed mammal, which soon could be used to treat humans.

"Recent discussion about using CRISPR to correct genetic mutations in human embryos has rightfully generated considerable concern regarding the ethical implications of such an approach," said Charles Gersbach, associate professor of biomedical engineering at Duke University. "But using CRISPR to correct genetic mutations in the affected tissues of sick patients is not under debate.”

For the study, the researchers used AAV, the most common virus used to deliver genes, as the delivery vehicle of the therapeutic tools. The team then programmed the CRISPR/Cas9 system to remove the dysfunctional exon from the mouse with DMD.

The process has led the animal’s natural repair system to fix the remaining gene to build a functional version of exon. Results show the mouse experienced correction of muscles, including in the heart, which is important as heart failure is a common cause of death for DMD patients, researchers said.

The method using CRISPR could potentially be used in a larger patient population, they added. However, Gersbach said further works are needed before using the technique for human therapy.

"But these results coming from our first experiments are very exciting,” he stated. “From here, we'll be optimising the delivery system, evaluating the approach in more severe models of DMD, and assessing efficiency and safety in larger animals with the eventual goal of getting into clinical trials."