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Monday, September 17, 2007 - Page updated at 12:00 AM

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Health panel discusses death of patient in Targeted Genetics study

Seattle Times business reporter

BETHESDA, Md. — A top-level scientific panel today discussed in painstaking detail the last moments of Jolee Mohr, who died after her knee was injected with an experimental gene therapy developed by Seattle's Targeted Genetics, but it failed to answer the key issue posed by her husband.

"The biggest question I have is, would my wife still be alive today if she had not participated in the study?" said Robb Mohr, addressing the panel toward the end of the four-hour session.

"We don't know," responded Howard Federoff, chair of the Recombinant DNA Advisory Committee (RAC) at the National Institutes of Health. He added that the panel would "reserve judgment" until all data is gathered, possibly by the group's next meeting in December.

Despite nearly eight weeks of study since the Illinois woman died July 24, scientists are still not in agreement on the immediate cause of death. And the role of Targeted Genetics' drug is also still in dispute.

They do agree that her immune system was wrecked, leading to a massive fungal infection and death. But some experts pondered whether death came from the infection attacking her liver, or from a large, tumorlike concentration of blood that displaced her organs and crushed her lungs. The source of the mass, called a hematoma, is unknown.

"She may have died with liver disease, but not necessarily of liver disease," said Leonard Seeff, of the National Institute of Diabetes and Kidney Diseases in Bethesda.

Mohr's tissue samples are still being analyzed at the University of Chicago, where scientists seek to determine whether the Targeted Genetics drug — designed to weaken the immune system in the joints in order to reduce the inflammation that leads to arthritis — spread beyond her knee.

The Targeted Genetics drug was designed to stay where it was injected. The drug consists of a gene riding on an adeno-associated virus (AAV), a carrier many scientists find promising because of its apparent mildness.

If AAV is found guilty of uncontrolled propagation beyond the knee or heavy toxicity, it would deal a heavy blow to Targeted Genetics — whose pipeline relies on AAVs — and to the whole field of gene therapy.

Mohr's death underscores the question of whether gene therapy, a biotechnology frontier in which no therapy has yet been approved, should be tried in patients with nonterminal conditions.

Questions also arose about whether she was properly informed by the researchers of the risks and benefits of participating in the trial.

Robb Mohr's lawyer, Alan Milstein, maintains that Jolee Mohr was unduly exposed to a very risky therapy.

Jolee Mohr, who was 36 when she died, had participated in another rheumatoid arthritis experimental trial, for Amgen's drug Enbrel, and had gone through other therapies to treat the condition, said Dr. Kyle Hogarth, the physician who attended to her at the University of Chicago Medical Center intensive care unit where she passed away.

At least 500 patients have been exposed to AAV-related therapies, and there have been 34 adverse event reports possibly related to the gene therapy, said Jacqueline Corrigan-Curay, acting executive secretary of the RAC panel. So far Mohr's death is the only one associated with the vector.

While the Chicago team has to grapple with limited tissue samples and doesn't expect to conclude the tests in less than three to four weeks, it managed to detect a small portion of the drug in spleen and liver tissue. The proportion is similar to results obtained — and deemed safe — in Targeted Genetics clinical and preclinical data.

The company says the findings underscore its claim that the drug didn't contribute to Mohr's death.

"It was very positive," said spokeswoman Stacie Byars.

Researchers still have to check blood and other samples, said Karen Frank, the pathologist at the University of Chicago hospitals conducting the study.

Mohr's lawyer, Milstein, has a different view. "I think it's significant that they found that data on the liver and the spleen," he said.

Robb Mohr, for his part, is anxious to see the end of the investigation. "I feel confident that the University of Chicago will get to the bottom of this."

Ángel González: 206-515-5644 or agonzalez@seattletimes.com

Copyright © 2007 The Seattle Times Company

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