First gene-editing therapy tested on man with metabolic disease
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 try 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. “I’m willing to take that risk. Hopefully it will help me and other people.”
Signs of whether it’s working may come in a month; tests will show for sure in three months.
Toying with nature
If it’s successful, it could give a major boost to the fledgling field of gene therapy. Scientists have edited people’s genes before, altering cells in the lab that are then returned to patients.
But these methods can be used for only 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
This time, the gene tinkering is happening in a precise way inside the body. It’s like sending a mini-surgeon along to place the new gene in exactly the right location.
“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 going back, 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 one independent expert, Dr. Eric Topol of the Scripps Translational Science Institute in San Diego.
Fewer than 10,000 people worldwide have these metabolic diseases, partly because many die very 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.
Madeux, who now lives near Phoenix, is engaged to a nurse, Marcie Humphrey, whom he met 15 years ago in a study that tested this enzyme therapy at UCSF Benioff Children’ s Hospital Oakland, where the gene editing experiment took place.
He has had 26 operations for hernias, bunions, bones pinching his spinal column, and ear, eye and gall bladder problems. Last year he nearly died from a bronchitis and pneumonia attack.
A gene-editing tool called CRISPR has gotten a lot of recent attention, but this study used a different one called zinc finger nucleases. They’re like molecular scissors that seek and cut a specific piece of DNA.
Bulletproof technology?
The therapy has three parts: the new gene and two zinc finger proteins. DNA instructions for each part are placed in a virus that’s been altered to not cause infection but to ferry them into cells. Billions of copies of these are given through a vein.
They travel to the liver, where cells use the instructions to make the zinc fingers and prepare the corrective gene. The fingers cut the DNA, allowing the new gene to slip in. The new gene then directs the cell to make the enzyme the patient lacked.
Only 1 percent of liver cells would have to be corrected to successfully treat the disease, said Madeux’s physician and study leader, Dr. Paul Harmatz at the Oakland hospital.
“How bulletproof is the technology? We’re just learning,” but safety tests have been very good, said Dr. Carl June, a University of Pennsylvania scientist who has done other gene therapy work but was not involved in this study.