Gene-Therapy Death Linked To Immune System's Reaction to Protein

AP 26jan01

PHILADELPHIA -- Researchers believe the death of an Arizona teen in a botched gene-therapy experiment was caused by a massive immune-system reaction associated with a protein used in the study.

University of Pennsylvania scientists say the protein was intended to carry new genes into Jesse Gelsinger's damaged liver, but instead triggered the immune-system response, which ultimately led to a coma and organ failure.

Tests in monkeys suggest that the immune system tried to destroy the foreign protein so much that it ended up eliminating proteins that cause blood to clot.

Mr. Gelsinger's Sept. 17, 1999, death, the first known to have been caused by gene therapy, resulted in a lawsuit against the university and potential action by the Food and Drug Administration against lead researcher James M. Wilson.

Dr. Wilson, director of Penn's Institute for Human Gene Therapy, discussed the findings at a closed-door medical symposium attended by several hundred gene-therapy researchers earlier this month in Snowbird, Utah.

He declined to comment until the findings are published in a medical journal, but several scientists told the Philadelphia Inquirer about the results.

"He did a nice piece of detective work and made an extremely important observation," said Jeffrey S. Chamberlain, a University of Washington researcher. "It's a safety feature that we now have to look at."

An attorney representing the family of Mr. Gelsinger, 18 years old, expressed disappointment in the findings. In November, the family settled a wrongful death lawsuit with Penn for an undisclosed sum.

In March, the FDA accused Dr. Wilson of violating safety regulations. He faces an FDA action that aims to strip him of his right to conduct clinical trials in the U.S.

The FDA ordered Dr. Wilson and the school to halt human drug trials.

He has also been accused of having a conflict of interest because a company he established funded part of the research.

Mr. Gelsinger suffered from an inherited disorder that inhibits nitrogen processing in the body. The disorder usually kills boys at a young age, but Mr. Gelsinger controlled his condition with drugs and a low-protein diet.

Researchers hoped to correct the problem by injecting into his liver a cold virus that had been modified to carry a gene that would control the condition.

But 24 hours after the therapy began, his condition went downhill. After two days, he slipped into a coma. He eventually was taken off life support