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.

comparison scan of brain i i

Brain scans of two boys with ALD. The scans on the left (A) are from a patient who received gene therapy; the one on the right (B) did not. The white areas represent the brain damage caused by the disease. The arrow on the left points to an area that showed some damage, but receded over the course of the therapy. Click on the image to see how the brains progressed over time. Image courtesy of Science/AAAS hide caption

itoggle caption Image courtesy of Science/AAAS
comparison scan of brain

Brain scans of two boys with ALD. The scans on the left (A) are from a patient who received gene therapy; the one on the right (B) did not. The white areas represent the brain damage caused by the disease. The arrow on the left points to an area that showed some damage, but receded over the course of the therapy. Click on the image to see how the brains progressed over time.

Image courtesy of Science/AAAS

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.