The preliminary report on the death of Jesse Gelsinger of Tucson, Ariz., strongly suggests that an infusion of corrective genes, incased in a weakened cold virus, led to the unusual immune system failure that caused multiple organ failure, said James M. Wilson, director of the University of Pennsylvania Institute for Human Gene Therapy.
Gelsinger is believed to be the first person to die as a direct result of gene therapy.
Researchers said they still did not understand specifically why Gelsinger, who had a gene disorder but was relatively healthy when he began the therapy, died four days after receiving the treatment.
The case is likely to revive a debate about using patients in gene-therapy trials who are not close to death. The trial involving Gelsinger was the first in the country to use relatively healthy people.
Gelsinger came to Penn Sept. 13 for treatment of ornithine transcarbamylase deficiency, a genetic disorder that leaves the body unable to produce enzymes that remove ammonia from the body. Doctors at Penn used a catheter to inject a large dose of genes engineered to make the enzymes into an artery to Gelsinger's liver, using the cold virus to carry the genes inside his cells.
Gelsinger's father, Paul, said his son knew there was a chance he could die from participating in the study, but he accepted the odds because he wanted to help himself and others.
Seventeen other patients had been through the procedure without ill effects, and Paul Gelsinger said he encouraged his son to participate.
But 24 hours after the therapy began, Jesse's condition went downhill rapidly. After two days, he was in a coma. His face was swollen and his body was jaundiced. He was taken off life support four days after the trial began.
The researchers said they found no evidence that a mistake in making or delivering the gene drug or other error contributed to Gelsinger's death. They also said none of the animal studies done before Gelsinger's treatment and none of the tests done on human volunteers predicted his crisis.
Penn's preliminary, 337-page report was sent Wednesday to the federal Office of Recombinant DNA Activities, which will discuss the findings at its quarterly meeting next week.
Penn's study has been halted and the Food and Drug Administration decided in October to halt two separate experiments by Schering-Plough trying gene therapy as a treatment for liver cancer and for colorectal cancer that spreads to the liver. Those studies also used relatively high doses of the adenovirus to carry new genes into the liver.
Gelsinger had a relatively mild form of OTC deficiency. Most babies born with the disease die within a few days of getting protein. But the gvernment has not approved testing in babies.
Gelsinger had been through three comas with the disease, but it was under control with a restricted diet and drugs.
After Penn reported Gelsinger's death, ORDA asked some 70 investigators doing human trials with adenoviruses to report any side effects. Practically all have responded, said ORDA director Amy Patterson, and the data are being reviewed by a panel of experts.