Six Children With Rare Diseases Successfully Treated, Researchers Say
Six children with rare genetic diseases were successfully treated using gene therapy that was delivered with a modified form of the AIDS virus, researchers said Thursday.
HIV, which causes AIDS, is proving a boon to gene therapy because the ability to infect cells that makes the virus so dangerous has also rendered it an efficient agent for delivering replacement genes into a patient.
The results of the two gene-therapy studies were published online Thursday by the journal Science. They are among a flurry of recent reports to demonstrate the potential of gene therapy in treating illnesses after several setbacks more than a decade ago chilled interest in the approach.
Three of the children were born with a hereditary disease called metachromatic leukodystrophy, or MLD, a neurological disorder that in its most severe form emerges in the second year of life, attacks the brain and is typically fatal by age 5. The three children, who were treated before experiencing any MLD symptoms, were developing normally as long as 21 months after the condition would typically emerge, researchers said.
"They're normal kids," said Luigi Naldini, director of the Milan-based San Raffaele Telethon Institute for Gene Therapy and leader of the research. "They have started kindergarten. They have normal IQs."
The three other children, with a hereditary immune system disorder called Wiskott-Aldrich syndrome, were successfully treated with the same technique.
In all six children, replacing a broken gene with a normal one "completely prevented the onset or the progression of the disease," Dr. Naldini said. It's too early to say whether the effect of one-time treatment will be sustained. He said the findings are "preliminary but encouraging."
Gene therapy generally involves giving patients healthy genes to correct faulty ones that are causing genetic disorders. The technique uses delivery vehicles called vectors that are fashioned from inactivated viruses to carry their payloads to the nucleus of cells.
The approach developed by Dr. Naldini and his colleagues "hijacks the ability of HIV to infect stem cells and uses it for clinical benefit," said Jason Gardner, a co-author of the studies and head of regenerative discovery medicine at GlaxoSmithKline PLC. In vectors derived from HIV, the virus is stripped of its disease-carrying characteristics before therapeutic genes are inserted.
Treating the two hereditary diseases required replacing defective genes in blood stem cells, Dr. Naldini said. He and his colleagues drew the children's own blood and administered the gene therapy outside the body before infusing blood with the corrective genes back into their bodies.
In some gene-therapy trials the corrective genes are taken up by only a fraction of the targeted cells, undermining the treatment's effect. In the new studies, however, as many as 90% of the cells converted to healthy cells, a level of efficiency that amounts to "almost a complete re-engineering of the cell," he said. The HIV-derived vector was "the key for achieving these results."
Rigorous efforts to check for side effects have so far proven the vector and the treatment to be safe, he added, but much longer follow-up is required.
James Wilson, a gene-therapy researcher at University of Pennsylvania, said the efficiency of the gene transfer was "outstanding - much better than what I thought could be achieved using this approach," but the extent of benefit remains to be determined.
The research was supported by the Telethon Foundation, an Italian charity interested in gene therapy, and by Glaxo, which has an option to move the treatment to commercial development.
Write to Ron Winslow at email@example.com