44-year old Brian Madeaux is the first-ever patient to receive gene editing therapy inside his body in order to cure the metabolic disease Hunter Syndrome.

For the first time in medical history, in-human gene editing has finally been attempted by scientists.

On Wednesday, the Associated Press (AP) reported that a in-human gene editing procedure was tried for the first time by U.S.-based scientists. Where in the past cells were genetically edited externally and then introduced to the patient, this treatment actively changed the DNA of the patient in his bloodstream.

The procedure was done on Monday in California to a 44-year-old British patient Brian Madeux, who is suffering from a rare genetic disorder called Hunter Syndrome. It was said that through an IV, Madeux received billions of copies of a corrective gene and zinc finger nucleases (ZFNs), a genetic tool that cut his liver’s DNA in the perfect places so that the corrective gene could modify dysfunctional cells.

According to the report, the first results of the experiment are expected to come out within a month. However, it will take around three months for the scientists to confirm if the procedure is successful.

Madeux referred to the experience as humbling. He said:

“It’s kind of humbling. I’m willing to take that risk. Hopefully it will help me and other people.”

While this is not the first case of human gene editing, previous gene editing has always taken place outside of the patient’s body. Thus, Madeaux’s case is the first of its kind in the history of medicine.

Gene Editing DNA to Cure Hunter Syndrome

According to research studies, Hunter Syndrome (MPS II) is a very rare, inherited genetic disorder that is caused by a missing or malfunctioning enzyme in the human body. The lack of the said enzyme leads to the build-up of certain complex molecules in harmful amounts.

The massive amounts of these harmful molecules can cause permanent, progressive damage that affects the appearance, mental health, physical abilities, and organ function of the person suffering from MPS II. Most notably, the patient’s metabolism cannot break down certain carbohydrates.

To date, there is no known cure for Hunter Syndrome which mainly occurs in boys as young as 18 months. Should the experiment conducted on Madeaux came out as a success, it would be considered as a major achievement with significant impact on the study of gene therapy.

Therapies that involved gene editing have made significant progress in past years. However, making genetic changes outside of the human body has its limitations. While such procedure allows researchers to conduct treatments without undesired effects, the experiments are only limited to conditions involving cells that could be altered externally like some blood cancers.

In Madeaux’s case, the corrective genes will work on their own like mini surgeons.

They are expected to reach the patient’s liver where zinc finger proteins will cut the gene responsible for the condition and then insert a healthy gene copy. Once done, the corrected gene is expected by the scientists to produce the enzyme that will control the build-up of harmful substances in Madeaux’s body.

The treatment was delivered by Sangamo Therapeutics, a California-based clinical-stage biopharmaceutical company which focuses on genomic therapies, and was received by Madeaux at UCSF Benioff Children’s Hospital in Oakland. In a statement to AP, Dr. Sandy Macrae, President of Sangamo Therapeutics, explained:

“We cut your DNA, open it up, insert a gene, stitch it back up. Invisible mending. It becomes part of your DNA and is there for the rest of your life.”

The promise that in-body gene editing holds is undeniable. However, it should be remembered that this new technology signals the start of human gene therapy. Once the procedure has been completed, there is no turning back. An edited genetic code can’t be altered back to its original form.

Despite the unknown consequences of the experiment, experts like Dr. Howard Kaufman, a Boston scientist on the National Institutes of Health panel that approved the studies, expressed positive support for the new technology.

“So far there’s been no evidence that this is going to be dangerous,” Dr. Kaufman said. “Now is not the time to get scared.”

How the Gene Editing Procedure Works Inside the Body

The procedure made use of what they referred to as zinc finger nucleases. ZFNs are synthetic proteins used for gene targeting. Like CRISPR-Cas9, ZNF functions in a similar way, by acting like molecular scissors that seek and cut specific pieces of DNA.

The in-body gene editing technique conducted on Madeaux has three components: the new genes and the two zinc finger proteins.

The DNA instructions for each part were placed in a virus that’s been altered to become non-replicating, non-pathogenic to not cause infection to the body. The virus will transport the new gene and ZFN into the cells. Billions of copies of these parts were given to Madeaux through a vein.

Once inside the body, the virus will travel to the liver. The cells will then use the instructions to make the zinc fingers and prepare the corrective gene. The ZFNs will then cut the damaged DNA to give room for the new gene to slip in. Once everything is in place, the new gene will instruct the cells to make the enzyme that Madeaux’s body lacked.

Dr. Paul Harmatz, Madeaux’s attending physician and the leader of the study said that only one percent of liver cells has to be corrected for the treatment to work and treat the disease.

Dr. Hamatz will monitor Madeaux’s enzyme level in the next three months followed by a liver biopsy to know if the corrected gene has been integrated and are producing the enzyme needed by the body. For now, experts will have to wait for the outcome of the experiment patiently.

Would you take a similar procedure to fix a condition like Hunter Syndrome? What sort of ailment would you have to have to consider going through gene editing treatment?