A YEAR after 18-year-old Jesse Gelsinger died following experimental gene therapy, researchers are beginning to understand what went wrong. Their work may help to prevent similar tragedies in the future.
Savio Woo of the Mount Sinai School of Medicine in New York opened the conference by recounting how Gelsinger died after he was injected with an adenovirus carrying a gene to treat his liver disorder. The incident sent shock waves through the field, and similar trials were quickly halted.
Federal agencies criticised the leader of the trial, James Wilson of the University of Pennsylvania, for not reporting adverse reactions in other patients, for example (New Scientist, 18 December 1999, p 9). But during the investigation, the National Institutes of Health's Recombinant DNA Advisory Committee learned that many other researchers had also failed to notify them of complications in gene therapy trials.
The manner of Gelsinger's death took scientists by surprise in a number of ways. Although the virus was injected directly into his liver, it infiltrated several other organs as well. And while liver inflammation was considered the most likely side effect, Gelsinger died from a widespread inflammatory reaction. Closer examination showed his blood had high levels of IL-6, a protein that promotes inflammation.
Now Wilson and his colleagues have done experiments in mice and monkeys to help them understand what went wrong. They found that in both animals, the infused virus left the liver and reached high levels in the spleen, lymph nodes and bone marrow. Even within the liver, the virus tended to accumulate in the Kupffer cells, which interact with the immune system, rather than in the main kind of liver cell, hepatocytes-which were the intended targets.
At least one of these unintended hosts contributed towards inflammation. Spleen cells in mice treated with the modified adenovirus produced IL-6 within hours. "They were cranking out this protein e
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Contact: Claire Bowles
claire.bowles@rbi.co.uk
44-207-331-2751
New Scientist
16-Jan-2001