[aftermathman]

http://seattletimes.nwsource.com/htm...928_tgen18.htm

"Fungus infection killed Targeted Genetics patient

By Ángel González

Seattle Times business reporter

New details about the death of a patient in a Targeted Genetics clinical trial are steering suspicion away from the virus used to deliver genes into the patient's cells, but it's still unclear whether the Seattle-based company's therapy was responsible.

Jolee Mohr, who died July 24 after being injected with a dose of Targeted Genetics' arthritis therapy, suffered a massive fungus infection that indicated her immune system was compromised, The Washington Post reported Friday.

In addition to Targeted Genetics' product, the 36-year-old Illinois woman was taking several anti-arthritis drugs that depressed the immune system in order to fight the disease, said the story, which cited a doctor participating in the medical investigation into her death.

The immune problem may indicate that the adeno-associated virus (AAV) used by Targeted Genetics to transfer genes into the patient's cells is not to blame. Reports of Mohr's death surprised many researchers, who until then saw the virus as safe.

"If this turns out to be true, it would probably allow other AAV trials to move forward," said Dr. Mark Kay, a gene-therapy expert at Stanford University.

The U.S. Food and Drug Administration said late last month that it was investigating the trial and stepping up its watch over similar experiments. An FDA spokeswoman said Friday the agency couldn't provide any additional information.

Targeted Genetics has said it doesn't have enough information yet to draw conclusions as to the cause of the patient's death, and that her illness was not "consistent" with other patients' reactions. The company didn't respond to a request for comment Friday.

The symptoms described in the Post story differ from another gene-therapy fatality, the death of Jesse Gelsinger in 1999 during clinical trials at the University of Pennsylvania.

Gelsinger died of a massive immune reaction provoked by an adenovirus, a more vigorous virus than the AAV used by Targeted Genetics. Gene therapy uses viruses to transfer disease-fighting genes into the patient's own cells.

Experts wondered whether Mohr's death might cast a permanent cloud over gene therapy's most promising delivery method. There are 29 AAV trials supervised by the FDA, according to the agency.

But now suspicion shifts to whether the combination of drugs that Mohr received — which are designed to combat arthritis by reducing immune response — overtaxed the immune system, said David Miller, an analyst with Seattle-based Biotech Stock Research.

Another possibility is that the Targeted Genetics' product propagated its immune-reducing effect outside of the patient's joints, its targeted area.

"There's nothing conclusive yet," Miller said. "You can't just blame Targeted's drug."

Alan Milstein, an attorney representing the Mohr family, said Targeted Genetics' drug could still have played a part in the patient's death even if the vector didn't trigger an immune response similar to Gelsinger's case.

"The problem with gene transfer to date is that scientists cannot control the expression of the gene," said Milstein, who represented Gelsinger's family in its legal fight against the University of Pennsylvania and is an expert on clinical trial litigation.

"We're exploring whether or not there was gene expression outside of the target area. Given that the purpose of the gene was immune suppression, if it did express itself outside of the target area that would create a potential for disaster for a subject like Mrs. Mohr," he said.

Even though the viral vectors used in Gelsinger's and Mohr's cases were different, there are "similarities," he said.

"You've got a human-subject experiment operating under the label of 'gene therapy,' " Milstein said. "I think what Jesse Gelsinger and Mrs. Mohr had in common is that neither understood the risks of participating in the experiment."

Neil.

[paula_w]

FYI

Alan Milstein represented the GDNF trial participants and the family in the first gene therapy death. We interviewed him on GRC at the time.

http://grassrootsconnection.com/milstein.htm

Paula