Early results boost hopes for historic gene editing attempt

Early results from a historic gene editing study have shown encouraging signs that the treatment may be safe, and could achieve at least some of its hoped-for effects.

Scientists stress that it is too soon to know whether the technique to permanently change a person’s DNA in order to cure a disease will ultimately succeed.

The results are from the first human test of gene editing in the body – in this case, tackling a genetic disorder called Hunter syndrome that often kills people in their teens.

In two patients who received a medium dose of the treatment, urine levels of large sugar compounds that are the hallmark of Hunter syndrome had fallen by half, on average, four months later – a possible sign the treatment is working.

Two others who received a low dose have seen little change in these sugars so far.

There is 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 their sugars have declined consistently since treatment suggests it might be.

Study leader Dr Joseph Muenzer of the University of North Carolina at Chapel Hill said that he cannot absolutely say the result was due to a treatment effect, but acknowledged that the drop is “really encouraging”.

The main goal of early treatment studies is to test safety, though researchers also look for hints that the therapy is working.

Dr Muenzer revealed the results at a conference in Greece.

He consults for the treatment’s maker, California-based Sangamo Therapeutics.

Company president Dr Sandy Macrae said tests will reveal more in about five months, but the change in the middle-dose group so far “looks really good”.

He said: “The most rational explanation for this is that what we hoped was going to happen, has happened.”

Dr Howard Kaufman, a Boston scientist and member of a US National Institutes of Health panel that reviewed the study before it began, said the results are “exciting”, and suggest that gene editing is working to some degree, without safety concerns so far.

Dr Matthew Porteus, a genetics expert at Stanford University who consults for two other companies developing gene therapies, said more time is needed to see how the patients’ immune systems continue to react to the treatment and whether the effects last. But he added that, based on the early results, “I would be excited about continuing to push along”.

Gene editing is intended as a more precise way to carry out gene therapy – knocking out a bad gene or supplying a good one that is missing. Doctors hope it will help address a host of diseases that cannot be treated at present.

In November, a man from Phoenix, Arizona with Hunter syndrome became the first person to test this inside the body.

Brian Madeux lacks a gene that makes an enzyme which breaks down certain large sugar compounds called GAGs. These build up in cells and cause havoc throughout the body.

Through an IV feed, Mr Madeux received many copies of a corrective gene as well as a gene-editing tool called zinc finger nucleases to help place it in a precise spot in his DNA.

He was one of the two patients given a very low dose of the treatment, as human testing requires extreme caution.

In the case of Mr Madeux and the other low-dose patient, levels of the tell-tale sugar compounds in urine rose 9% on average after four months.

Dr Muenzer said it is hard to know whether this is a significant change. This is because little is known about the biology of these compounds, including whether they fluctuate during the day or before or after meals.

A liver biopsy on one patient given a low dose of the therapy found no evidence that the gene editing had occurred, but Sangamo scientists said this dose is far below the level at which such signs had been detected in research on primates.

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

Dr Muenzer said that one important goal had been met: the treatment seems safe. There were two serious side effects – one patient was taken to hospital for bronchitis and another for an irregular heartbeat – but those were deemed due to their disease and pre-existing conditions, not the gene treatment.

Two more patients have been given the highest dose being tested – 10 times the starting dose – making up a total of six patients in the study.

The next step is to start taking patients off the weekly enzyme treatments they have been receiving to see if the gene therapy has changed their bodies so they can make enough of the enzyme themselves.

More results are expected to be revealed in February.