Gene-Editing Procedure Used for First Time on Man with Hunter Syndrome
등록일 2019년 01월 07일 목요일
수정일 2017년 11월 16일 목요일
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A pioneering medical procedure was performed on 44-year-old Brian Madeux who underwent gene editing on Monday, the first time it was done on a human, making medical history.In a clinical trial from Sangamo Therapeutics, zinc-finger nucleases, which are microscopic gene editing tools, were inserted in his body, The Atlantic reported.

The editing tools aimed to cure him of Hunter syndrome, a genetic syndrome that causes several syndromes such as joint stiffness, developmental delay, and breathing problems. Also known as Mucopolysaccharidoses II, or MPS II, it is a rare disorder that causes progressive damage to the body's cells.

Missing enzyme

Madeux was hooked to an IV that delivered a gene editor into his bloodstream with copies of a corrected gene to replace the mutation he carries that is responsible for his condition, CNN reported.Dr.Edward Conner, the senior vice president and chief medical officer of Sangamo Therapeutics, said the infusion takes place between two and three hours.

The gene editing tool seeks to correct the man's condition wherein he is missing an enzyme that breaks down mucopolysaccharides chains of sugar molecules used to build connective tissues.According to Science Mag, the replacement copy of the gene inserted in Madeux used gene editing to snip the DNA helix of liver cells in a specific place near the promotor, or on-off switch, in the gene for a protein called albumin.

By inserting the DNA for the new gene supplied by the researcher with the DNA scissors of the gene editor, the cells fix the repair.The activity of the gene would then be controlled by the powerful albumin promotor to turn the modified cells into a factory that makes the enzyme missing in Hunter syndrome patients.

Conner compared the situation of a Hunter syndrome patient to a house where garbage accumulates over time.The enzyme helps remove the trash.A Hunter syndrome patient suffers from sugar build up which happens in several different tissues like the brain and the heart due to the absence of the enzyme.It results in physical symptoms such as bone and joint malformation, hearing problems, and heart and breathing difficulties, Terri Klein, the interim president and director of development and operations at the National MPS Society, said.

Progressive damage to body

Widespread damage throughout the body occurs as the disease progresses, including the bones, respiratory system, heart, joints, and central nervous system.Klein pointed out that the syndrome has no known cure, but it can be managed and treated with enzyme replacement therapies.

Despite going through enzyme replacement therapies, patients with the Hunter syndrome still suffer from progressive damage to their lungs, bones, and heart.Most of them die of airway obstruction, heart failure, and upper respiratory infection before they reach 20 years old, Dr.Paul Harmatz, the principal investigator of the study, said.

The zinc-finger nucleases inserted in the body of the patient were engineered to find a specific stretch of DNA where a new gene can be inserted.Doctors know exactly where it is going in the genome, Chester Whitley, a principal investigator on the Sangamo clinical trials, said.The body has 30,000 genes, and doctors using the technology have to be precise in where the editing tool acts.Other than the zinc-finger nucleases, the infusion on Madeux contained billions of copies of the gene he is missing.

Zinc-finger nucleases are distinct from CRISPR, a newer gene-editing tool which could also find precise stretches of DNA.But in the US, CRISPR for gene-editing in the body has not yet reached the clinical trials stages in the US.

No reversal of all damages in body

The researchers noted that even if Madeux will have treatment, it will not be able to reverse all of the damage in the body.However, it can stop the ailment's progression and eliminate the need for expensive and time-consuming enzyme-replacement therapies currently used by Hunter syndrome therapy patients to manage the disorder.

The treatment was first tested in mice and non-human primates.The National Institutes of Health vetted the safety of the treatment and the clinical trial.The infusion on Madeux was done on Monday.Doctors observed the patient for 24 hours in the hospital.When he left for his hotel on Tuesday, he looked fine and did not have any problems, so far.

Harmatz, the principal investigator and a pediatric gastroenterologist at the UCSF Benioff Children's Hospital Oakland, said that in two to three months, he and Conner should know if Madeux's treatment worked.Klein noted that what Madeux went through is a new world of science that needed someone to be on the front line. "Brian has risen to the occasion," he pointed out.

Most of the Hunter syndrome patients are males.Conner estimated that one in every 100,000 to 170,000 boys is born with the genetic disease.But in extreme cases, it may affect girls.

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