In a first, gene therapy halts a fatal brain disease
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 medicine’s greatest villains: HIV.
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 percent. Some who survive are left with lifelong disabilities.
Now a new study, published online in the New 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 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 in order 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 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. The research began with a determined mother, Amber Salzman, who was an executive with a PhD 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.”