On New Year’s Eve, Science magazine published three articles (here, here, here) simultaneously that successfully used CRISPR/Cas9 gene editing to treat mice that have Duchenne muscular dystrophy (DMD).
DMD is a rare, genetic disease that affects approximately 1 in 3,600 boys in the US. It’s caused by a mutation in the dystrophin gene, which generates a protein that is essential for normal muscle function. DMD causes the body’s muscles to weaken and degenerate, leaving patients deformed and unable to move. It’s a progressive disease, and the average life expectancy is around 25 years. Though there are treatments that help prolong or control the onset of symptoms, there is no cure for DMD.
Three studies use CRISPR to treat DMD in mice
For those suffering from this debilitating disease, there is hope for a new therapy – a gene therapy that is. Three groups from UT Southwestern, Harvard, and Duke, used the CRISPR gene editing method to remove and correct the mutation in the dystrophin gene in mice with DMD. All three used a safe viral delivery method to transport the CRISPR/Cas9 gene editing complex to the proper location on the dystrophin gene in the mouse genome. There, the complex was able to cut out the mutated section of DNA and paste together a version of the gene that could produce a functional dystrophin protein.
This technique was tested in newly born mice as well as in adult mice by injecting the virus into the mouse circulatory system (so that the gene editing could happen everywhere) or into specific areas like the leg muscle to target muscle cells and stem cells. After the gene editing treatment, all three studies found restored expression of the dystrophin protein in heart and skeletal muscle tissue, which are the main tissues affected in DMD. They were also able to measure improved muscle function and strength in the animals.
This is really exciting news for the DMD field, which has been waiting patiently for an approved therapy. Currently, two clinical trials are underway by BioMarin and Sarepta Therapeutics, but the future of these drugs is uncertain. A gene therapy that could offer a “one-time cure” would certainly be a more attractive option for these patients.
Strong media coverage of DMD studies
It’s important to note that none of these gene editing studies reported a complete cure. However, the results are still very promising. Charles Gersbach, senior author on the Duke study, commented, “There’s a ton of room for optimization of these approaches.”
The implications of these studies are potentially huge. These studies were covered by prominent news outlets like Science News, STAT News, The Scientist, and The New York Times.
What I appreciate about the news coverage of the DMD studies is the balanced tone. Reporters highlight the promise of the research, yet they also stress the need for more work in mice and larger animals. Each article uses the words “safe” or “safety,” which shows that both scientists and journalists recognize the importance of rigorous testing before moving to large human trials.
What’s next
Even so, CRISPR gene editing for DMD may reach clinical trials within a few years. Charles Gersbach told STAT News that human trials could begin once safety is fully evaluated. He noted that researchers still need to understand how the human immune system will respond to CRISPR delivered into the body. He added, “If we do this right, we will only need one treatment. This method, if proven safe, could be applied to patients in the foreseeable future.”
Eric Olson, senior author of the UT Southwestern study, expressed a similar view. “To launch a clinical trial, we need to scale up, improve efficiency, and assess safety. I think within a few years, those issues can be addressed.”
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