A team of scientists at the UCSF Pediatric Hospital in Oakland, California, and the US biotechnology company Sangamo Therapeutics are 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’s syndrome, a genetic hereditary disease. In this condition, the organism does not properly break down the long chains of sugar molecules (glycosaminoglycans), so that they accumulate to injure various tissues and organs, sometimes in a lethal way. 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 organism to decompose the sugar molecules in the proper way, but Madeux accepted to be the guinea pig of this pioneering experiment, since he suffers “every second of the day”, according to his own words.
Doctors say that it will take a month to know 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 one works inside the organism of a living person.
Genetic cut and paste
Scientists have modified the patient’s DNA to be able to permanently synthesize the enzymes that your body needs. To do this, they have injected billions of copies of a corrective gene that are directed to the cells of the liver and inserted into a specific point of their genetic code, in addition to two proteins that work like molecular scissors that cut the 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 nucleases with zinc fingers (ZFN, for its acronym in English), something more expensive and developed before. Both allow inserting a corrective gene at the desired point in the genetic code.
A risky treatment
This therapy can go wrong. Some of the people to whom DNA has been inserted have died, and the defective genetic edition ends up in cancer at times. But Brian Madeux is willing to risk it, since he has already gone through 26 surgeries and suffers unceasingly.
Throughout the trial, the new gene will be inserted in 1% of Madeux’s liver cells, which, if all goes well, will not have to continue receiving weekly transfusions of enzymes. In this case, Sangamo Therapeutics will test the technique in nine other sick volunteers to assess their safety. If it is effective in patients with Hunter syndrome, it could be applied in other disorders caused by a defect in a single gene, such as hemophilia B.