In a medical first, doctors on Monday injected a man with an experimental treatment designed to edit his genes while they are still in his body, hoping to cure him of a formerly incurable disease.
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According to the Washington Post's "To Your Health," the patient, 44-year-old Brian Madeux, has Mucopolysaccharidoses II (MPS II), or Hunter syndrome, a metabolic disease that causes progressive cell damage.
People with Hunter syndrome lack the gene necessary to manufacture an enzyme that breaks down a particular type of carbohydrates. Those carbohydrates accumulate in cells, causing damage to the brain, bones, heart, lungs, and nervous system.
Symptoms tend to start presenting at around age 1 and then progressively worsen. Patients with the most severe version of the disease usually pass away during adolescence, "To Your Health" reports.
While Hunter syndrome is not curable, it can be treated with weekly infusions of the missing enzyme. However, treatment can cost anywhere from $100,000 to $400,000 a year, and it does not prevent brain damage.
Details of the new therapy
The new therapy, developed by Sangamo Therapeutics, utilizes zinc finger nucleases, a tool that the Associated Press likens to "molecular scissors" that target and cut sections of DNA. Sangamo Therapeutics is funding studies to test the therapy as a treatment for two metabolic diseases—including Hunter syndrome—as well as hemophilia, AP reports. The technique is distinct from another gene-editing tool, CRISPR.
In the attempt to cure Madeux, physicians at University of California-San Francisco Benioff Children's Hospital Oakland, injected him with a virus carrying DNA instructions for two zinc finger proteins and for the gene that Madeux currently is missing. The virus is intended to carry the instructions to Madeux's liver, where cells should manufacture the zinc fingers and develop the new gene. At that point, the zinc fingers should slice Madeux's DNA and insert the gene.
According to Paul Harmatz, Madeux's physician and leader of the study, just 1% of the cells in the liver have to be altered to treat the disease. Sandy Macrae, the president of Sangamo, summed up the process, saying, "We cut your DNA, open it up, insert a gene, stitch it back up. Invisible mending. … It becomes part of your DNA and is there for the rest of your life."
The infusion process took between two to three hours, Edward Conner, SVP and CMO of Sangamo, said. After receiving the infusion on Monday, Madeux remained in the hospital for 24 hours for observation. He is currently back home, where he is doing well, "To Your Health" reports.
Researchers will have to wait several weeks before they can assess whether the procedure has worked. They will also assess whether the procedure has reversed any tissue damage or improved Madeux's ability to walk and breathe.
The procedure is a one-time-only attempt. If it doesn't work, physicians won't be able to try again: Because of the initial infusion, Madeux is now immune to the virus used to deliver the gene-editing tool to his cells.
Ultimately, researchers hope to use the tool to cure young children with Hunter syndrome, AP reports. "In older patients, some of those changes from the disease would be already locked in and wouldn't change by this treatment," Macrae said. "There would be some benefits, but this is really a first step to being able to treat children."
According to AP, the process carries risks. The gene editing is permanent, which means any resulting mistakes cannot be repaired. In addition, researchers say the virus could cause Madeux's immune system to attack his own body, or that the new gene could unintentionally affect other genes.
Other experts worry that the virus could work its way into other places in the body, potentially including sperm—where it could potentially affect future generations. But physicians say they have implemented genetic safeguards to ensure the gene can work only in the liver.
According to Eric Topol of the Scripps Translational Science Institute, another potential risk is that "you could unleash a genome to start a cancer process." But Topol said that studies should continue despite the risks because, without a successful gene therapy, these diseases are incurable.
Reactions to the therapy
Macrae said that the trial "open[s] up a whole new field of medicine." He added, "You can imagine all the diseases that now become possible to treat when you can put in a new copy of the gene, or turn it up or turn it down."
Separately, Topol called the trial "a very important milestone," saying that he's "never seen anything move at this velocity" (AP/Sacramento Bee, 11/15; Eunjung Cha, "To Your Health," Washington Post, 11/16; Scutti, CNN, 11/16).
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