Nov. 5 (Bloomberg) -- Two 7-year-old boys with a fatal brain disease who couldn’t get bone marrow transplants were saved by scientists whose gene therapy technique may let doctors treat other incurable disorders.

Doctors in Paris delivered the gene into the boys’ bodies using HIV, the virus that causes AIDS. The virus, stripped of genetic material that makes it toxic, integrates permanently into the DNA of cells it enters, scientists said. That means the modified gene remains in the blood-forming stem cells for the life of the patient, according to a report in the journal Science.

Two years after the experimental treatment, the neural damage has been halted or reversed and the two boys attend school and lead normal lives, said Nathalie Cartier, the study’s lead author. The treatment was cited as an example of a “comeback for gene therapy,” after years of setbacks, in an editorial in the journal.

“Their disease is completely stabilized, they are fine and there’s no reason this should change,” Cartier, research director at the French National Institute for Health and Medical Research in Paris, said in a telephone interview yesterday. If more studies confirm the results, she said, “We think gene therapy could become a first-line treatment. It’s definitely a strategy that could be applied to other conditions.”

Today’s report “represents a long-sought rewarding achievement in the field of gene therapy,” wrote Luigi Naldini, a researcher in Milan, Italy, in the editorial accompanying the study.

Other Uses Possible

The two unrelated 7-year-olds suffer from a condition called adrenoleukodystrophy, or ALD, and couldn’t be treated with a bone marrow transplant, the standard therapy, because no matching donors could be found. Instead, doctors in Paris tried a different technique, removing the boys’ own blood-forming stem cells and inserting into them a gene that makes a vital protein missing in people with ALD, according to today’s journal report.

The gene therapy method may soon be tried in two more common blood diseases, thalassemia and sickle cell anemia, as well as two neurological conditions, Wiskott-Aldrich syndrome and metachromatic leukodystrophy, Cartier said.

About one in 18,000 boys is born with ALD, according to the Stop ALD Foundation, based in Houston. The genetic disorder is triggered by lack of a protein called ABCD1, which helps break down chains of fatty acids that form in the brain. The deficiency damages the myelin sheath that surrounds and protects nerve cells, leading to impairments in movement and thinking.

ALD is the condition described in “Lorenzo’s Oil,” the 1992 movie starring Nick Nolte and Susan Sarandon and based on a family’s real-life search for a cure for their son.

Death at Adolescence

The disease typically appears when boys are 4 to 10 years old and leads them to become withdrawn and forgetful, to perform poorly in school and to develop a range of symptoms, including impaired vision and hearing, poor coordination and dementia, according to the U.S. National Institute of Neurological Disorders and Stroke, based in Bethesda, Maryland. Without treatment, most boys with ALD die by the time they reach adolescence.

The disease is passed to boys on the X chromosome they inherit from their mothers. Girls generally don’t get the condition, because they also inherit a second X chromosome with a normal gene. Less commonly, a milder form of the disease can affect adults.

Halting Disease

If the condition is diagnosed early enough, before the myelin has been greatly damaged, doctors can halt further injury by giving patients bone marrow transplants. The existing marrow is knocked out and replaced by new marrow that contains repaired blood stem cells. Those cells make others that cross into the brain and help restore myelin production.

Transplants have provided a way to reverse the course of the disease, Cartier said. They can help if they are performed early and involve donors whose tissue type matches the patients’, she said.

The two boys treated in Paris were seen early in the course of the disease by Patrick Aubourg, a pediatric neurologist at the Hospital Saint-Vincent de Paul in Paris. Both boys had relatives with ALD and were being monitored for signs of the illness, Cartier said.

“Usually when the families come to see Patrick with neurological symptoms, the lesions are too severe and no treatment is available,” Cartier said.

No Match

In another way, the boys weren’t so lucky: No donors could be found whose bone marrow closely matched theirs. Instead, they became the first patients to be treated with the new gene therapy technique that Aubourg, Cartier and their colleagues had been developing.

They collected blood from the boys’ bone marrow, inserted a functional copy of the ABCD1 gene into it and injected the altered blood back into the boys’ bodies.

What made their treatment unusual was that the gene was delivered inside a modified copy of HIV, the virus that causes AIDS. The virus had been stripped of any genetic material that could make it toxic.

HIV belongs to a family called lentivirus and differs from viruses used in other gene therapy trials, Cartier said. Its advantage is that it integrates permanently into the DNA of cells it enters. That means the modified gene remains inside the blood-forming stem cells for the life of the patient, helping make myelin, Cartier said.

‘Incredibly Exciting’

The research was funded by the French and German governments and by charities, including the Stop ALD Foundation. The group’s president, Amber Salzman, said she lost a nephew to ALD five years ago and has a son and nephew who were treated with bone marrow transplants. She said she hopes to extend the trial run by the French doctors to the U.S.

“This is incredibly exciting news,” Salzman said in a telephone interview yesterday. “This approach could be applied to other diseases that don’t have a good therapy.”

The form of virus used in the experiment was made by Cell Genesys Inc., now a unit of BioSante Pharmaceuticals Inc. of Lincolnshire, Illinois. BioSante is negotiating with scientific groups that may license the technology, Chief Executive Officer Stephen Simes said in a telephone interview.

In the journal editorial, Naldini wrote that using this virus to deliver the gene therapy may lessen the risk of causing leukemia seen in other experimental gene therapy failures.

To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net.

Last Updated: November 5, 2009 19:01 EST