Teenager's death in gene therapy trial at Penn probably caused by massive reaction to protein used in study.
Penn scientists said the protein, which coated the adenovirus used to carry new genes into 18-year-old Jesse Gelsinger's damaged liver, triggered an immune system response which ultimately led to coma and organ failure. Tests in monkeys confirmed this chain of events.
Gelsinger's death in September 1999,the first known to have been caused by gene therapy, resulted in a lawsuit against the university and prompted the FDA to indefinitely suspend Penn's gene therapy trials last March. In addition, James Wilson, MD, director of the Philadelphia university's Institute for Human Gene Therapy, faces an FDA action that aims to bar him from ever conducting another human trial in the United States. Wilson also was accused of having a conflict of interest because a company he established funded part of the research.
Wilson declined comment on the new findings until they are published in a medical journal. But he discussed them at a closed-door medical meeting attended by several hundred gene therapy researchers earlier this month in Snowbird, UT. Some attendees confirmed the findings to The Philadelphia Inquirer.
Donald Kohn of the University of Southern California said the results call into question the safety of newer viral vectors. Unlike older adenovirus vectors, which had only a portion of their viral genes removed, viral genes are completely extracted from the new "gutted adenoviruses." These vectors do, however, retain the protein coats that have been implicated in Gelsinger's death. "If you give huge amounts [of gutted adenoviral vector], it may be a problem," Kohn said.
An attorney representing the family of Gelsinger expressed disappointment at the findings. In November, the family settled a wrongful death lawsuit with Penn for an undisclosed sum. "What Dr. Wilson also seems to have confirmed is that this clinical trial should never have started," Alan Milstein said.