Sun Sentinel Palm Beach Edition
Scientists try first gene editing in body
California man receives billions of copies of a corrective gene and a genetic tool to cut his DNA in a precise spot in a groundbreaking attempt to cure disease. Signs of the experiment’s success should be known in about a month.
OAKLAND, Calif. — Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person’s DNA to cure a disease.
The experiment was done Monday in California on 44-year-old Brian Madeux. Through an IV, he received billions of copies of a corrective gene and a genetic tool to cut his DNA in a precise spot.
“It’s kind of humbling” to be the first to test this, said Madeux, who has a metabolic disease called Hunter syndrome. “Hopefully it will help me and other people.”
Signs of whether it’s working may come in a month. If successful, it could give a major boost to gene therapy. Scientists have edited people’s genes before, altering cells in the lab that are then returned to patients. There also are gene therapies that don’t involve editing DNA.
But these methods can be used only for a few types of diseases. Some give results that may not last. Some others supply a new gene like a spare part but can’t control where it inserts in the DNA, possibly causing a new problem like cancer.
This time, the gene tinkering is happening in a precise way inside the body.
“We cut your DNA, open it up, insert a gene, stitch it back up. Invisible mending,” said Dr. Sandy Macrae, president of Sangamo Therapeutics, the California company testing this for two metabolic diseases and hemophilia. “It becomes part of your DNA and is there for the rest of your life.”
That also means there’s no way to erase any mistakes the editing might cause. “You’re really toying with Mother Nature” and the risks can’t be fully known, but the studies should move forward because these are incurable diseases, said Dr. Eric Topol of the Scripps Translational Science Institute in San Diego.
Protections are in place to help ensure safety, and animal tests were encouraging, said Dr. Howard Kaufman, a Boston scientist on the National Institutes of Health panel that approved the studies.
“So far there’s been no evidence that this is going to be dangerous,” he said.
Fewer than 10,000 people worldwide have these metabolic diseases, partly because many die young. Those with Madeux’s condition, Hunter syndrome, lack a gene that makes an enzyme that breaks down certain carbohydrates. These build up in cells and cause havoc throughout the body.
Patients may have frequent colds and ear infections, distorted facial features, hearing loss, heart problems, breathing trouble, skin and eye problems, bone and joint flaws, bowel issues and brain and thinking problems.
Weekly IV doses of the missing enzyme can ease some symptoms but cost $100,000 to $400,000 a year and don’t prevent brain damage.
Madeux, who now lives near Phoenix, has had 26 operations for hernias, bunions, bones pinching his spinal column, and ear, eye and gall bladder problems.
Gene editing won’t fix damage he’s already suffered, but he hopes it will stop the need for weekly enzyme treatments.
Safety issues plagued some earlier gene therapies. One worry is that the virus might provoke an immune system attack. In 1999, 18-year-old Jesse Gelsinger died in a gene therapy study from that problem, but the new studies use a different virus that’s proved much safer in other experiments.
Another worry is that inserting a new gene might have unforeseen effects on other genes.
Finally, some fear that the virus could get into other places like the heart, or eggs and sperm where it could affect future generations. Doctors say built-in genetic safeguards prevent the therapy from working anywhere but the liver.
This experiment is not connected to more controversial work being debated to try to edit genes in human embryos to prevent diseases before birth — changes that would be passed down from generation to generation.