Gene editing: A promising future treatment for DMD

Using a new gene-editing technique, a team of scientists at UT Southwestern Medical Center stopped progression of Duchenne muscular dystrophy (DMD) in young mice.

If efficiently and safely scaled up in DMD patients, this technique could lead to one of the first successful genome editing-based treatments for this fatal, muscle-wasting disease.

This work represented the first major finding of the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center at UT Southwestern, which was established in 2015 with $7.8 million in funding from the National Institutes of Health.

“Because it eliminates the cause of the disease, this gene-editing technique is different from other therapeutic approaches,” said Dr. Eric Olson, Chairman of Molecular Biology, Co-Director of the Wellstone Center, and Director of the Hamon Center for Regenerative Science and Medicine. In addition, Dr. Olson holds the Annie and Willie Nelson Professorship in Stem Cell Research, the Pogue Distinguished Chair in Research on Cardiac Birth Defects, and the Robert A. Welch Distinguished Chair in Science.

In 2014, Dr. Olson’s team first used this technique – called CRISPR/Cas9-mediated genome editing – to correct the mutation in the germ line of mice and prevent muscular dystrophy. This paved the way for novel genome editing-based therapeutics in DMD. It also raised several challenges for clinical applications of gene editing. Since germ line editing is not feasible in humans, strategies would need to be developed to deliver gene-editing components to postnatal tissues.

Normal Muscle
Dystrophic Muscle
Corrected Muscle
 

Using a new gene-editing technique, UTSW researchers stopped progression of Duchenne muscular dystrophy in mice. These images show how normal and dystrophic muscle looks under immunofluorescence imaging, and then muscle corrected by this method.

To test the therapeutic potential of CRISPR/Cas9-mediated genome editing in vivo, researchers delivered gene-editing components to the mice via adeno-associated virus 9 (AAV9). DMD mice treated with this technique produced dystrophin protein and progressively showed improved structure and function of skeletal muscles and the heart. The gene-editing approach permanently corrected the DMD mutation that causes the disease in young mice.

Now, the research team is working to apply this gene-editing technique to cells from DMD patients and in larger preclinical animal models.