Thursday April 27 2:33 PM ET
By Maggie Fox, Health and Science Correspondent
WASHINGTON (Reuters) - In what some experts are calling the first true gene therapy success, French researchers said on Thursday they had treated two infant boys for a rare, inherited immune system disorder.
The boys have human severe combined immunodeficiency (SCID) X1, which leaves them without any working immune system. Patients usually live out their short lives in sterile "bubbles" because any infection would overwhelm them.
Dr. Alain Fischer of the Necker Hospital in Paris and colleagues said they had managed to restore their immune systems using gene therapy.
"Both enjoy normal growth and psychomotor development. No side effects have been noted," they wrote in their report, published in the journal Science.
Although they do not know how long the new genes will last and continue to provide an immune system for the boys, the researchers said their results "pave the way" for the same approach to be used in other genetic diseases.
"I think this is the first evidence ever that gene therapy does anything," said Dr. David Nelson, an expert in inherited immune diseases at the U.S. National Cancer Institute in Bethesda, Maryland, in a telephone interview.
"This is really good stuff."
Missing Master Control Gene Replaced
SCID X1 patients are missing a master control for the immune system, a cell receptor that turns on the different immune system cells, including T cells that flag and destroy invaders and natural killer cells.
The defect is inherited on the X chromosome, which only males have, so it is easier than some other genetic defects to track down and try to correct.
Attempts to just introduce an improved version of the gene into patients' bodies have not worked, so Fischer's team tried a new approach, using stem cells.
Stem cells are nursery cells, found in this case in the bone marrow. They give rise to all the different kinds of blood cells, including the immune system cells.
Bone marrow is now routinely mined for stem cells to treat a range of diseases, including leukemia.
Fischer's team took bone marrow cells from the two boys, aged 8 and 11 months at the time, and purified out the stem cells. They do this by looking for a marker known as CD34, which is believed to be a pointer to stem cells.
They nursed these cells along in a special cocktail of compounds meant to help the stem cells thrive and multiply, and also to make them more amenable to genetic engineering.
Added into the mix was a virus carrying a healthy version of the gene the boys needed, called the gamma-c cytokine receptor sub-unit. The virus, a retrovirus, injected the new gene into the stem cells.
After three days, the mixture was purified and the infected cells put back into the boys.
Results Within 15 Days
Within 15 days the researchers saw results. The boys started producing immune cells and chemicals. One boy who had suffered from diarrhea and skin lesions had his symptoms clear up and both went home after three months.
The researchers think the stem cells carrying the new and improved gene had a survival advantage over the defective immune cells. They worked better, so they thrived.
Each boy has been home for nearly a year without treatment. They have normal levels of T, B, and natural killer immune cells and have been successfully vaccinated against tetanus, diphtheria, and polio -- vaccinations that would not have worked for the boys before.
Fischer said a third patient had also gone through the treatment and looked healthy after four months.
Word of his work has leaked out in various journals and at meetings, and has been the subject of interested discussion.
Ted Friedmann, director of the program in human gene therapy at the
University of California San Diego, has also described the experiment as
the first gene therapy approach to show true benefit.