UT Southwestern scientists, reportedly for the first time, have used CRISPR gene editing to halt the progression of Duchenne muscular dystrophy (DMD) in a large mammal.

The study, published recently in Science, documents unprecedented improvement in the muscle fibers of dogs with DMD.

These results, they suggest, provide a strong indication that a lifesaving treatment for DMD may be in the pipeline.

DMD is caused by a mutation that inhibits the production of dystrophin, a protein critical for muscle function.

Researchers used a single-cut gene-editing technique to restore dystrophin in muscle and heart tissue by up to 92 percent of normal levels. Scientists have estimated a 15 percent threshold is needed to significantly help patients, explains a media release from UT Southwestern Medical Center.

“Children with DMD often die either because their heart loses the strength to pump, or their diaphragm becomes too weak to breathe,” says Dr Eric Olson, director of UT Southwestern’s Hamon Center for Regenerative Science and Medicine.

“This encouraging level of dystrophin expression would hopefully prevent that from happening,” he adds.

The study establishes the proof-of-concept for single-cut gene editing in dystrophic muscle and represents a major step toward a clinical trial. Already Dr Olson’s team has corrected DMD mutations in mice and human cells by making single cuts at strategic points of the mutated DNA.

The latest research applied the same technique in four dogs that shared the type of mutation most commonly seen in DMD patients. Scientists used a harmless virus called adeno-associated virus (AAV) to deliver CRISPR gene-editing components to exon 51, one of the 79 exons that comprise the dystrophin gene.

CRISPR edited the exon, and within several weeks the missing protein was restored in muscle tissue throughout the body, including 92% correction in the heart and 58% in the diaphragm, the main muscle needed for breathing, the release continues.

“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,” states Dr Leonela Amoasii, lead author of the study and Assistant Instructor of Molecular Biology in Dr Olson’s lab. “But we have more to do before we can use this clinically.”

The lab will next conduct longer-term studies to measure whether the dystrophin levels remain stable and to ensure the gene edits do not have adverse side effects.

Olson hopes the next step beyond dogs is a clinical trial. In the meantime, Olson’s recent work has spawned a biotechnology company, Exonics Therapeutics Inc, which is working to further optimize and bring this technology to the clinic, per the release.

[Source(s): UT Southwestern Medical Center, Science Daily]