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New gene therapy could cure a deadly disease that stops the heart from beating

New gene therapy could cure a deadly disease that stops the heart from beating


CRISPR strikes back

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Illustration by James Bareham / The Verge

Scientists have successfully tweaked the DNA in human heart cells to correct mutations that cause a deadly disease. If the gene-editing technique is proven safe, it could permanently cure children with a genetic disorder that leaves them wheelchair-bound by their early teens.

The genetic disease targeted in this study is called Duchenne muscular dystrophy (DMD), a disorder that affects about one in 5,000 males and causes the progressive wasting away of skeletal and heart muscles. Researchers took cells from patients with the disease, and used the gene-editing tool CRISPR-Cas9 to correct up to 60 percent of the mutations that cause the disease. That was enough to allow heart tissue engineered from those edited cells in a petri dish to beat again as a healthy heart would, according to a study published today in Science Advances.

“This is a rare and exciting moment in scientific time.”

In the past few years, scientists have been using gene editing to try to treat or cure a variety of debilitating genetic disorders, such as Hunter syndrome and hypertrophic cardiomyopathy. Today’s study tackles another nasty disease, raising hopes that a cure might be just years away. It’s a step forward in the development of gene therapies, which tinker with genes in order to treat or prevent diseases.

“This is a rare and exciting moment in scientific time when one can correct an error in the human DNA that can cause a devastating disease,” says study author Eric Olson, a molecular biologist at the University of Texas Southwestern Medical Center.

The gene-editing tool used in this study, called CRISPR-Cas9, is based on a defense mechanism bacteria used to ward off viruses by cutting off bits of their DNA. Scientists have engineered that mechanism to prevent mice from going completely deaf, or to edit immune cells of patients with lung cancer, to help them fight the disease. Now, scientists are unleashing CRISPR on yet another genetic disorder. DMD is caused by more than 3,000 different mutations in the so-called dystrophin gene, which disrupt the production of the protein dystrophin. This protein is key for making muscle fibers strong and safe from injury as skeletal and heart muscles contract and relax. Patients with DMD usually have to use a wheelchair by the age of 13, and can die in their mid to late 20s, Olson says. “This disease has defied every therapy that’s been tested so far,” he says. “It’s a really tough one.”

“This disease has defied every therapy that’s been tested so far.”

In the study, Olson and his colleagues took blood samples for patients with DMD and created a type of cell that can produce all of the body’s cell types, called induced pluripotent stem cells. These cells were then turned into heart muscle cells, which had the genetic mutations responsible for DMD. Most of these genetic mutations are grouped together in “hotspot” areas in the dystrophin gene. So the researchers used CRISPR to correct the defective segments of DNA within or nearby those hotspots. Once edited, the heart muscle cells were able to start producing the key dystrophin protein, Olson says.

The researchers also put those heart muscle cells together in a 3D scaffold, to measure how the cells performed. Not only did the technique allow the edited cells to produce the protein, it also restored muscle function, allowing the engineered heart muscle to beat. That’s important because patients with DMD die because their heart stops contracting, Olson says. The researchers believe that their gene-editing method could rescue muscle function in up to 60 percent of patients.

Genome editing corrects the cardiac abnormalities in patient’s engineered heart tissue. 
Genome editing corrects the cardiac abnormalities in patient’s engineered heart tissue. 
Video: UT Southwestern Medical Center

“I’m surprised by how simple and effective this method turned out to be so far,” Olson says. CRISPR seems to have cut only the DNA spots it was supposed to, without making any so-called off-target edits, he says. But follow-up studies are needed to confirm that’s actually the case. The technique has been tested in live mice, as well as dogs, and appears to be working. The mice have been cured for at least a year: the animals keep producing the dystrophin protein and look “very healthy,” Olson says. Now, the technique has been proven effective even in human cells in a petri dish.

“This is only the beginning, but it’s very exciting to be able to go not at the symptoms of the disease, but at the cause of the disease and in principle, to permanently correct it,” he says. If studies continue to go smoothly, with promising results, clinical trials could start within a couple of years, according to Olson.

That could be life changing for patients with DMD. Olson says that one 25-year-old man with the disease got to see his own edited heart cells in a petri dish during the study. “He was able to look through the microscope and see his own cells producing the protein that his own body could never make,” he says. “It was incredible, very exciting — [an] exhilarating moment.”