Scientists have attempted to cure a patient with a rare genetic disorder by rewriting the DNA inside his body, in a first-of-its-kind therapy they hope could one day be applied to numerous other conditions including hemophilia and sickle cell disease.
The procedure, which took place on Monday at the University of California at San Francisco's Benioff Children's Hospital in Oakland, Calif., involved sending what the Associated Press described as “billions of copies of a corrective gene and a genetic tool to cut his DNA in a precise spot” into the patient's body. These edits are designed to enable the patient, 44-year-old Brian Madeux, to produce an enzyme that would counteract a metabolic disease he suffers from known as Hunter syndrome.
While there have been a few cases of doctors modifying a patient's genes in a lab and then putting them back into the patient, this is the first to attempt to edit them inside the body.
“This is opening up a whole new field of medicine,” said Sandy Macrae, president of Sangamo Therapeutics, which funded the trial. “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.”
Symptoms of Hunter syndrome often appear around the time a baby turns 1 and are progressive. Those who suffer from the disease are not able to break down certain substances that can lead to damage to the lungs, heart, brain and nervous system. Those with the most severe form die by their teenage years.
Macrae said the company's goal is to be able to treat children with the disease and that, if progress is satisfactory, tests could begin as soon as next year.
“In older patients, some of those changes from the disease would be already locked in and wouldn't change by this treatment,” he said in an interview with The Washington Post. “There would be some benefits, but this is really a first step to being able to treat children.”
Macrae said Madeux has returned home and that he understands the patient is doing well. Madeux's doctors will follow up in the coming weeks to see whether enough of the enzyme is being produced and whether any tissue damage is being reversed. Doctors will also look for improvements in the patient's walking ability and respiratory function.
Gene editing is one of the most exciting and active frontiers of medicine, and there are no fewer than 12 trials in progress using different techniques to treat diseases of the eye, blood and metabolism, according to scientists in the field. Until recently, the field had been almost at standstill after the death of a clinical trial volunteer named Jesse Gelsinger after a gene therapy procedure. But momentum has built up in the past few years with the invention of the CRISPR tool that allows for more precise editing of the genome.
Madeux's treatment involved a similar technology known as zinc finger nucleases (ZFNs). A third type of editing called transcription activator-like effector nucleases (TALENs) is also being tested for medical applications.
Eric Topol, a geneticist and cardiologist at the Scripps Translational Science Institute, called the new trial “a very important milestone.”
“I’ve been following medicine over 30 years. I’ve never seen anything move at this velocity,” Topol said of the gene therapy treatments that have moved into human testing in recent years.
But Topol cautioned that “we are in the earliest days” and that patients will have to be carefully monitored for years for safety. Among the biggest risks is “off-target” edits that could lead to a whole host of other issues beyond the disease the patient started with. Among the biggest risks, Topol said: “You could unleash a genome to start a cancer process.”
Right now, Topol said, we can deliver new genes into only a few parts of the body, which limits the types of diseases we can treat. These are the eyes, blood and liver. Madeux's treatment targeted the latter to stimulate production of the needed enzyme.
A growing number of scientists, including those at Sangamo, are trying to figure out how to modify genes in the brain. Macrae is excited as he explains how this would open up the possibility of treat devastating conditions including Alzheimer's, which affects 5.5 million Americans.
But, Macrae said, “before we all get overexcited we have to see this first step through.” We should know in a few months whether Madeux's treatment worked.