Gene Therapy Death Puzzles Scientists, Regulators
Reuters Online Service
Freitag, 10. Dezember 1999 00:22:00
Copyright 1999 Reuters Ltd. All rights reserved.@bThe following news report may not be republished or redistributed, in whole or in part, without the prior written consent of Reuters Ltd.
By Maggie Fox, Health and Science Correspondent
BETHESDA, Md. (Reuters) - Researchers said on Thursday they
were running batteries of tests and examining other trials to
see if they can find what killed a teenager during a gene
therapy experiment -- and whether their findings can protect
future patients.
The doctors at the University of Pennsylvania who conducted
the trial said they were looking at the possibility that
18-year-old Jesse Gelsinger, who died within days of getting the
experimental treatment, had some kind of viral infection that
made him unusually sensitive.
They are also looking at his genetic make-up, at the precise
genetics of the virus they used in the treatment, and at other
factors.
Gelsinger died in September after he became the 18th patient
in the trial, meant to test the safety of a potential gene
therapy treatment for a genetic liver disorder known as
ornithine transcarbamylase deficiency (OTC), a genetic defect
that causes ammonia to build up in the body.
He was the first person known to have died as a direct
effect of gene therapy which, while it has never been shown to
have cured anyone of any disease, was thought to be a relatively
harmless treatment.
Tried in a range of diseases from cancer to hemophilia, gene
therapy aims to replace missing or faulty genes, or to boost
certain genes. It has been found to help heart and artery
disease patients grow new blood vessels.
In Gelsinger's case, as in many other trials, the new genes
were carried into the body using a genetically modified
adenovirus -- one of the family of viruses that causes colds as
well as severe infections such as pneumonia.
"At no time during or prior to this trial did we in any way
expect to see what we saw in Jesse Gelsinger," Dr. James
Wilson, one of the researchers who ran the trial, told a
three-day hearing at the National Institutes of Health.
He and colleagues outlined the many animal tests that his
team had done, as well as the results from the 17 patients who
went before Gelsinger in the OTC trial.
There was nothing unusual about the reaction of the patients
to the gene therapy, they said, until Gelsinger died.
They said the tissues in his body showed he had suffered a
huge revolt of his immune system. It destroyed his liver and
spleen and badly damaged his lungs and other organs.
Regulators at the Food and Drug Administration (FDA), who
worked with the Pennsylvania team, said they also did not
suspect anything might go wrong. However, they outlined a few
lapses made by the researchers in reporting adverse events such
as suggestions of liver damage, no matter how transient.
The researchers apologized for these but said they did not
think they failed to report anything that would have predicted
Gelsinger's death. "I don't think it would have had any
effect," Dr. Mark Batshaw of the Children's National Medical
Center in Washington, who worked on the Penn study, said.
Nonetheless, the FDA and the Recombinant DNA Advisory
Committee (RAC) of the NIH, which both have authority over gene
therapy trials, are proposing tighter restrictions on
researchers.
At a third day of hearings on Friday they will outline plans
to make researchers report all serious adverse events to both
the FDA and the RAC within 15 days.
The FDA usually carefully guards what researchers, and the
companies that often back them, regard as trade secrets, but the
RAC believes in making this information public in case it might
save patients' lives or health.
Industry objects. "A reporting system that entails the
reporting of all serious adverse events in an expedited manner
is inappropriate and unnecessary," the Biotechnology Industry
Organization said in a statement.
It said such adverse events -- which can range from a
temporary rise in liver enzymes to a deadly stroke -- are often
not caused by the treatment and reporting them before they are
fully understood could unnecessarily release trade secrets and
also confuse people.