Duchene muscular dystrophy (DMD) is a rare, but severe disorder that forces patients into wheelchairs and often leads to death by the age of 30. In a paper, published in Science Advances, researchers describe a newly developed CRISPR gene-editing technique that could potentially correct a majority of the 3,000 mutations that cause DMD by making a single cut at strategic points along the patient’s DNA. This treatment offers hope for one day creating the first treatment to the disease and could open up the doors for similar treatment approaches to other genetic diseases.
The technique, developed by UT Southwestern Medical Center scientists, involved the development of 12 guide RNAs to find mutation “hotspots” along the dystrophin gene to help restore cardiac function to near-normal levels in human heart muscle tissue. The dystrophin gene, which is mutated in patients with DMD, helps strengthen muscle fibers. By eliminating abnormal splice sites along the gene, the researchers observed significant improvements in its dystrophin protein product when tested in induced pluripotent stem cells from multiple patients with large deletions, point mutations, or duplications within the DMD gene.
"In fact, we found that correcting less than half of the cardiomyocytes (heart muscle cells) was enough to rescue cardiac function to near-normal levels in human-engineered heart tissue," said Dr. Chengzu Long, lead author of the study and Assistant Professor of Medicine at New York University Langone Health.
Pending federal approval, it is anticipated that clinical trials will begin this year in the U.S. starting with blood disorders. In the meantime, the team plans to continue testing the method to ensure it does not have adverse side effects and to find ways to further improve the precision of the guide RNAs.
Image: Dr. Eric Olson shows DMD patient Ben Dupree the dystrophin protein (red) produced in gene-edited heart muscle cells taken from Mr. Dupree's blood. A new study from Dr. Olson shows the CRISPR-Cas9 gene-editing tool can potentially correct a majority of the 3,000 types of mutations that cause DMD. Image courtesy of UT Southwestern Medical Center.