In a first, gene therapy halts a fatal brain disease

HopeBrandon Rojas, who has ALD, with his mother and father in their home in Dover Plains, New York. His younger brother, Brian, received treatment in a clinical trial .NYT  

For the first time, doctors have used gene therapy to stave off a fatal degenerative brain disease, an achievement that some experts had thought impossible.

The key to making the therapy work? One of the medicine’s greatest villains: HIV.

The disease

The patients were children who had inherited a mutated gene causing a rare disorder, adrenoleukodystrophy, or ALD. Nerve cells in the brain die, and in a few short years, children lose the ability to walk or talk. They become unable to eat without a feeding tube, to see, hear or think. They usually die within five years of diagnosis.

The disease strikes about one in 20,000 boys; symptoms first occur at an average age of 7. The only treatment is a bone-marrow transplant — if a compatible donor can be found — or a transplant with cord blood, if it was saved at birth.

But such transplants are an onerous and dangerous therapy, with a mortality rate as high as 20%. Some who survive are left with lifelong disabilities.

Now a new study, published online in theNew England Journal of Medicine, indicates that gene therapy can hold off ALD without side effects, but only if it is begun when the only signs of deterioration are changes in brain scans.

The study involved 17 boys (the disease strikes males almost exclusively), ages 4 to 13. All got gene therapy. Two years later, 15 were functioning normally without obvious symptoms.

“To me, it seems to be working,” said Dr. Jim Wilson, director of the gene therapy programme at the University of Pennsylvania’s Perelman School of Medicine, who was not involved in the new study.

One of the remaining two boys died; his disease progressed so rapidly that gene therapy could not stop it. The other withdrew from the study to have a bone-marrow transplant. He died of complications from the procedure.

The study opens new avenues for using gene therapy to treat brain diseases, said Dr. Theodore Friedmann, a gene therapy pioneer at the University of California San Diego School of Medicine.

“Many think the central nervous system is intractable and unapproachable,” he said. This study proves them wrong.

Where it began

The research began with a determined mother, Amber Salzman, who was an executive with a Ph.D. in mathematics at GlaxoSmithKline. In 2000, her nephew was diagnosed with ALD, a disease she had heard of only in the movie,Lorenzo’s Oil.He was “this wonderful sweet brilliant kid,” Salzman said. “All of a sudden he loses his abilities. He crumbles in front of your eyes.”

She had her one-year-old son tested and found that he had the mutated gene, as did another nephew. She looked into Lorenzo’s oil, a difficult dietary regimen featuring a specially designed oil.