No decision yet on whether gene therapy caused death

The Seattle Times—BETHESDA, MD—September 18, 2007

A top-level scientific panel discussed in painstaking detail Monday 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 the group 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, visibly shaken as he addressed the panel toward the end of the four-hour session.

"We don't know," responded Howard Federoff, chairman 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 still don't agree on the immediate cause of death. The role of Targeted Genetics' drug, a treatment for rheumatoid arthritis, is also still in dispute.

They do agree Jolee Mohr's 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 mass of blood that displaced her organs and crushed her lungs. The source of the mass, called a hematoma, is unknown.

Mohr's tissue samples are still being analyzed at the University of Chicago, where scientists seek to determine whether the Targeted Genetics drug had spread beyond the 36-year-old woman's knee.

The drug aims to weaken the immune system in the joints to reduce the inflammation that leads to arthritis. But it was designed to stay where it's injected, without spreading.

The Targeted Genetics 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 of drug candidates relies on AAVs — and to the whole field of gene therapy.

The clinical trial has been suspended pending firm conclusions from the Chicago investigation.

Mohr's death underscores the question of whether gene therapy, a biotechnology frontier with no therapy yet approved, should be tried in patients with non-lethal diseases.

Robb Mohr's lawyer maintains that Jolee Mohr and others were unduly exposed to a very risky therapy.

But some panelists said that even though rheumatoid arthritis is not fatal, the chance to beat it was worth the risk associated with clinical trials.

The disease, which tends to focus on the joints, causes "pain and swelling and deformities," said Mary K. Crow, M.D., rheumatology research chief at New York's Hospital for Special Surgery. "It can cause significant disability."

Read the full story in The Seattle Times.