Revolutionary Gene Therapy Offers Hope for Duchenne Muscular Dystrophy

CRISPR/Cas9 gene editing platform able to remove Duchenne mutations in cells.

A recent development in the use of CRISPR/Cas9 technology could potentially improve the treatment of Duchenne muscular dystrophy, a fatal disease that affects about 1 in 5000 boys in the United States.

What is Duchenne Muscular Dystrophy?

Duchenne occurs through the mutation in the gene dystrophin, which makes a protein with the same name. Although there are hundreds of mutations in the dystrophin gene that can cause Duchenne muscular dystrophy, about 60% of people with the disease have a mutation with a specific hot spot in the gene.

Since the mutations cause abnormally low production of the dystrophin protein, it leads to the atrophy of muscles. Although there are medications that treat the symptoms, the disease is incurable.

Duchenne muscular dystrophy is the most common fatal childhood genetic disease, with symptoms that start in early childhood and gradually progress. In the 30 forms of muscular dystrophy, Duchenne muscular dystrophy is the most common.

The disease eventually leads to the loss of mobility and death from respiratory or heart failure as patients reach around 20-years-old. The study, which was performed at UCLA and published in Cell Stem Cell, used CRISPR/Cas9 to correct these genetic mutations.

Researchers took skin cells from patients who had mutations within the dystrophin gene hot spot. The cells were reprogrammed in order to create induced pluripotent stem cells (iPS), which can transform into any type of human cell while still maintaining the genetic code from the original person.

The work was performed at the Broad Stem Cell Research Center, an FDA compliant facility that is important for the process of preclinical research moving toward human clinical trials.

They then used the CRISPR/Cas9 gene editing platform to remove the Duchenne mutations in the iPS cells.

What is CRISPR/Cas9?

Back in 2012, researchers discovered that they could adapt the CRISPR/Cas9 system — a naturally occurring reaction that bacteria uses to fight viruses – to make cuts in human DNA sequences. This can act as a navigation system and can be programmed to seek out the mutation.

CRISPR/Cas9 also cuts mutations out of the genetic code and can even replace the mutation with normal genetic sequences in some instances.

The next step after the iPS cells were free from the Duchenne mutations was to differentiate the iPS cells into skeletal muscle and cardiac muscle cells. These cells were then transplanted into mice with the genetic mutation in the dystrophin gene.

The transplanted muscle cells were found to produce the dystrophin protein successfully.

The results of the study proved that this was the biggest deletion in the dystrophin gene using the CRISPR/Cas9 system. This study was also the first to be able to create human iPS cells that could directly restore functional muscle tissue in Duchenne patients.

"This work demonstrates the feasibility of using a single gene editing platform, plus the regenerative power of stem cells, to correct genetic mutations and restore dystrophin production for 60 percent of Duchenne patients," said co-senior author April Pyle.

The next step will be for researchers to develop different strategies to test the CRISPR/Cas9 platform to treat the disease in animals. As of now, the platform for Duchenne is not available for clinical trials.