A team of scientists from UCSF Children’s Hospital in Oakland (California) and the American biotechnology company Sangamo Therapeutics is making the first attempt to modify a person’s DNA within their own body and not in the laboratory.
The test aims to cure Brian Madeux, a 44-year-old man who suffers from Hunter syndrome, a hereditary genetic disease. In this condition, the body does not properly break down the long chains of sugar molecules (glycosaminoglycans), so that they accumulate to damage various tissues and organs, sometimes lethal. Brain damage, heart problems and constant infections are some of the problems that affect these patients, who have a poor quality of life.
The treatment of Hunter syndrome usually consists of a periodic replacement of the enzymes that allow the body to break down the sugar molecules in the proper way, but Madeux agreed to be the guinea pig in this pioneering experiment, as she suffers pain “every second of the day” , in his own words.
Doctors say that it will take a month to see if things are going well, and three months to see if the trial has worked. The results were a success in previous tests carried out in the laboratory, but it is the first time that work has been done inside the body of a living person.
Cut and paste genetic
Scientists have modified the patient’s DNA so that it is able to permanently synthesize the enzymes that your body needs. To do this, they have injected billions of copies of a corrective gene that target liver cells and are inserted at a specific point in their genetic code, in addition to two proteins that work like molecular scissors that cut fragments of DNA where this new genetic material will be inserted. “We cut the DNA, we open it, we insert the gene where we want it and we close it again,” says Dr. Sandy Macrae, president of Sangamo Therapeutics.
The genetic editing technique used has not been the best known CRISPR, but the so-called zinc finger nucleases (ZFN), somewhat more expensive and developed earlier. Both allow a corrective gene to be inserted at the desired point in the genetic code.
A risky treatment
This therapy can go wrong. Some of the people who have had DNA inserted have died, and faulty gene editing sometimes leads to cancer. But Brian Madeux is willing to risk it, since he has already undergone 26 surgeries and suffers incessantly.
Throughout the trial, the new gene will be inserted into 1% of Madeux’s liver cells, which, if all goes well, will no longer have to receive weekly enzyme transfusions. In this case, Sangamo Therapeutics will test the technique on nine other sick volunteers to assess its safety. If it is effective in patients with Hunter syndrome, it could be applied in other disorders caused by a single gene defect, such as hemophilia B.
