Early gene editing results inspire optimism

Therapy deemed safe, though results unclear

PHOENIX — Early, partial results from a historic gene editing study give encouraging signs that the treatment may be safe and having at least some of its hoped-for effect, but it’s too soon to know whether it ultimately will succeed.

The results, announced Wednesday, are from the first human test of gene editing in the body, an attempt to permanently change someone’s DNA to cure a disease, in this case a genetic disorder called Hunter syndrome, which often kills people in their teens.

In two patients who got a medium dose of the treatment, urine levels of large sugar compounds that are hallmarks of Hunter syndrome had fallen by half, on average, four months later, a possible sign the treatment is working. Two others who got a low dose have seen little change in these sugars so far.

There’s no way to know yet whether the change in the middle-dose patients is due to the gene editing or something else, but the fact that their sugars have declined consistently since treatment suggests it might be.

“I cannot absolutely say it’s a treatment effect” but the drop is “really encouraging,” said the study leader, Dr. Joseph Muenzer of the University of North Carolina, Chapel Hill.

Gene editing is intended as a more precise way to do gene therapy, to knock out a bad gene or supply a good one that’s missing. Doctors hope it will give a way to address a host of diseases that can’t be treated well now.

In November, a Phoenix-area man with Hunter syndrome, Brian Madeux, became the first person to test this inside the body. He lacks a gene that makes an enzyme that breaks down certain large sugar compounds called GAGs. These build up in cells and cause havoc throughout the body.

He was one of the two patients given a very low dose of the treatment, because this first-in-human testing called for extreme caution.

In Madeux and the other low-dose patient, levels of the telltale sugar compounds in urine rose 9 percent on average after four months. Muenzer said it’s hard to know whether this is a significant change; little is known about the biology of these compounds, including whether they fluctuate during the day or before or after meals.

Two other patients were given a middle dose that was twice what the first two patients received. Their GAG levels declined by 51 percent after four months, on average. Two of the main types of these sugars that accumulate in tissues declined 32 percent and 61 percent, respectively.

It is not yet known whether declines like these can improve patients’ health or slow the progression of the disease.

“This is not proof that this is a successful therapy yet, that these patients had enough gene editing to now supply them with the enzyme they need for the rest of their life,” Muenzer said.

But he said an important goal was met: the treatment seems safe.

Blood tests did not detect the missing enzyme. Scientists said this could be because any that was being made was rapidly used by cells rather than getting into the bloodstream, an explanation some outside experts agreed with. What counts, they said, was seeing the result of enzyme activity, the drop in sugars.

Matt York The Associated Press Brian Madeux brushes his horse at his home in New River, Ariz. Madeux was the first person in the world to participate in a gene editing attempt in his body.