Rare Disease Treated Using Gene Therapy
Researchers in France have successfully treated two young boys with a rare but fatal genetic disease. This marks a high point for the field of gene therapy after several well-publicized setbacks.
Patrick Aubourg leads the French research team. Since 1993, he's been working on a disease called X-linked adrenoleukodystrophy — or ALD. ALD is a devastating neurological disease, incapacitating and ultimately killing people who have it. Many people became familiar with ALD from the 1992 movie Lorenzo's Oil, which featured a young boy affected with this disease.
Viral Vectors
Since ALD is caused by a single gene, it's an ideal candidate for gene therapy. Put the repaired gene back into patient's cells, and that should fix the problem.
Simple in theory, but in practice, it's been extremely difficult. The biggest hurdle has been finding an efficient way to get the repaired gene into the cells of patients. One of the tricks involves attaching the gene to a virus. The virus acts as a vector, inserting the repaired gene into cells.
But the viral vectors can cause their own problems. In one case, another team of French researchers successfully treated several patients with a different single-gene disease, only to find that the vector caused some of the patients to develop leukemia.
Aubourg thinks he has now found a safer virus, and after treating two patients, the results are promising. As he and colleagues report in the Nov. 6 edition of Science, two patients have now been successfully treated.
"I use the term 'treated,' " says Aubourg. "I don't use the term 'cure' — treated. The disease has been arrested, not reversed, really."
But arresting the disease may be enough if the treatment is done before the disease progresses too far.
David Williams of Children's Hospital Boston says Aubourg's technique for getting the repaired gene into a patient's cells is the most efficient yet reported. But it's still not all that efficient.
"They have about 10 to 20 percent of the cells carry the new gene," says Williams. But, he adds, "that's enough, it appears, to arrest the progression of the disease."
Safety Issues
Williams also thinks Aubourg's new viral vector will be safer than others used in the past. Aubourg does not report any problems associated with the vector in his Science paper.
"Having said that, these patients are still only three years or so out from their therapy," says Williams. "So it's still possible that something would evolve, although there's no indication in the molecular analysis that it would evolve."
Other researchers are impressed with the French team's results. Jude Samulski, director of the gene therapy center at the University of North Carolina, says it should change the way ALD is treated.
"It's going to start a flurry of activity," says Samulski. Even though it's a rare disease, he says that at the University of North Carolina, they see a lot of kids with the disease. "And now that we know there's an approach that might work, we'll start trying it. Because if they can't get a bone marrow transplant, they've got nothing."
Bone marrow transplants have been shown to work with ALD patients, but the transplants are risky, and frequently there's no donor available.
Gene Therapy's Coming-Of-Age
Williams says the French results may mean gene therapy is finally coming of age.
"When gene therapy started, there were a lot of predictions that this was going to revolutionize medicine. It's been a long time to actually get it to work in humans"
If the treatment for ALD holds up, it might be the start of that revolution.
9(MDAyNzUwMDI2MDEyNTA3MTU5NzcyNTQyNA004))
MICHELE NORRIS, host:
After a series of setbacks, the field of gene therapy has taken an important step forward. A report out today describes work by researchers in France. They have successfully treated two young boys with a rare but fatal genetic disease.
As NPR's Joe Palca reports, this news is good for patients with this particular disease and for the entire field of gene therapy.
JOE PALCA: Finding the gene that causes a disease is just the start in finding a treatment for that disease. No one knows that better than Patrick Aubourg.
Dr. PATRICK AUBOURG (Professor of Pediatrics, University Paris-Descartes): 1993.
PALCA: 1993 is the year Aubourg published a key paper describing the single-gene defect that causes X-linked adrenoleukodystrophy or ALD. It's a devastating neurological disease, incapacitating and ultimately fatal. It's the disease affecting the young boy in the movie "Lorenzo's Oil."
In the years after he isolated the gene, Patrick Aubourg figured out how to repair it and began working on a way to put the repaired gene back into patients.
Enter Amber and Rachel Salzman. They are both mothers of children with ALD. They started a foundation called Stop ALD, committed to finding a treatment for the disease. When they heard about Aubourg's interest in gene therapy, Amber Salzman says she and her sister flew to Paris to meet with him, not so much to ask for his help - their children were past the point where they could benefit from gene therapy - but to see how they could help him.
Ms. AMBER SALZMAN (Co-Founder, Stop ALD): It's not that we in particular were gene therapy experts by any means. It's just, I think we took this relentless - whatever it is, we will make it happen.
PALCA: Salzman says she and her sister put Aubourg in contact with some American researchers who were developing a new technique for getting repaired genes into patients using something called a lentivirus. By 2006, Aubourg was ready to try the new technique with ALD patients. And now, as he writes in the journal "Science," he appears to have a successful treatment for the disease.
Dr. AUBOURG: I use the term treated. I don't use the term cure. Treated. The disease has been arrested, not reversed, really.
PALCA: But arresting the disease may be enough if the treatment is done before the disease progresses too far.
David Williams of Children's Hospital Boston says one of the biggest hurdles facing would-be gene therapies is getting enough of the repaired gene into patients' cells. Williams says Aubourg's approach seems to have cracked that problem.
Dr. DAVID WILLIAMS (Children's Hospital Boston): Even though they have about 10 to 20 percent of the cells apparently carry the new gene, that's enough. It appears to arrest the progression of the disease.
PALCA: One of the other big problems facing gene therapy has been safety. Another French team succeeded in treating a different genetic disease, only to discover that the virus they used to deliver their gene therapy gave their patients leukemia.
Williams says the new approach appears to have avoided that problem.
Dr. WILLIAMS: Having said that, these patients are still only three years or so out from their therapy. And so it's still possible that something could evolve, although there's no indication in the molecular analysis that it would evolve.
PALCA: Other researchers are impressed with the French team's results.
Dr. JUDE SAMULSKI (Director, Gene Therapy Center, University of North Carolina): Oh, I think it's going to change a lot.
PALCA: Jude Samulski is director of the Gene Therapy Center at UNC, the University of North Carolina. He expects many people will want to try the approach on ALD patients.
Dr. SAMULSKI: Even here at UNC, we see a lot of these kids. And now that we know there's an approach that may work, we'll start proposing it. Because if they can't get a bone marrow transplant, they have nothing.
PALCA: Bone marrow transplants have been shown to work with ALD patients, but the transplants are risky and frequently there's no donor available.
David Williams of Children's Hospital Boston says the French results may mean gene therapy is finally coming of age.
Dr. WILLIAMS: When gene therapy started, there was a lot of predictions that this was going to revolutionize medicine. And it's been a long time to get it to actually work in humans.
PALCA: If the treatment for ALD holds up, it might be the start of that revolution.
Joe Palca, NPR News, Washington. Transcript provided by NPR, Copyright National Public Radio.
