Woman who died after gene therapy had infection

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Woman who died after gene therapy had infection

Bloomington Pantagraph - IL*

By Rick Weiss

Washington Post

http://www.pantagraph.com/articles/2007/08/17/news/doc46c66d64cc99579

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WASHINGTON, D.C. — The 36-year-old McLean County native who died

last month after being treated with an experimental gene therapy was

infected with a fungus that usually causes only a mild illness.

But the infection spun out of control and ravaged her organs,

suggesting that her immune system was seriously impaired, said a

doctor who is part of the medical investigation.

Jolee Mohr's body also was teeming with a cold-sore virus that the

body normally keeps in check, another indication of a faltering

immune system. And because of a tear inside her abdomen — perhaps

caused by infection, perhaps by injury — she had an internal blood

clot the size of a watermelon.

No formal cause of death has been declared for Jolee Mohr, who died

July 24.

Mohr, a Bellflower native, and her husband Robb moved from McLean

County in 1996 and had lived in ville since 2000. They have a

5-year-old daughter, Toree.

Mohr had been generally healthy until July 2, when trillions of

genetically engineered viruses were injected into her right knee in

an experimental treatment for her rheumatoid arthritis.

The injected viruses were genetically modified so they would

suppress the immune system — which is responsible for the

inflammation of rheumatoid arthritis — only in her knee. Doctors

hope that tests on tissue specimens and blood samples will tell

whether the treatment's effects somehow spread from the joint to

other parts of Mohr's body.

The picture will be complicated, however, because Mohr was also

taking conventional immune-suppressing drugs for her arthritis. One

of those in particular, adalimumab, whose brand name is Humira, is

known to make patients susceptible to histoplasmosis, the kind of

fungal infection that Mohr had. Inexplicably, Mohr suddenly became

ill in July even though she had been taking that drug for years and

the fungus that causes histoplasmosis is ubiquitous in the area

where she lived.

" It's a major mystery,'' said Hogarth, who heads the intensive

care unit at the University of Chicago Medical Center, where Mohr

was transferred days before she died.

The company behind the medical experiment, Targeted Genetics of

Seattle, has said that the treatment has an excellent safety record

and that none of the more than 100 other volunteers who got the

injections suffered anything more than short-lived side effects.

Hogarth and about 20 other doctors and scientists are investigating

the death with help from experts in an immune system factor called

tumor necrosis factor-alpha, or TNF-alpha, which is suppressed by

the experimental genetic treatment and by Humira.

The autopsy was done with particular care, using sterile techniques

more commonly associated with surgery on the living because of the

importance of getting good clinical evidence, Hogarth said.

" Think `CSI,' without the criminal implications,'' he said, adding

that he suspects it will take one to two months to complete the

tests.

The fungus found throughout Mohr's body is Histoplasma capsulatum.

It is common in airborne dust and bird droppings in the Mississippi

and Ohio river valleys and generally causes a mild respiratory

illness when inhaled. But in people whose immune systems are

compromised — because of AIDS or cancer chemotherapy, for example —

the fungal cells can spread to other organs and blossom quickly into

fatal infections.

" It was in her liver. In the blood. It was essentially everywhere,''

Hogarth said.

It is not known whether Mohr's infection was recently acquired or

was old and recently reactivated. In healthy people, the immune

system walls off the fungal cells in structures called granulomas,

whose integrity is maintained by TNF-alpha. When TNF-alpha is

suppressed, the granulomas can dissolve and release the still-living

fungi.

Experts in gene therapy are eagerly awaiting the test results. A

link to the death would be a painful setback for the research field,

which attempts to treat diseases by giving people new genes.

" Gene therapy holds a great deal of potential,'' said Arthur

Nienhuis of St. Jude Children's Research Hospital in Memphis, who is

president of the American Society of Gene Therapy. He noted that

after more than a decade of failures and a handful of instances in

which gene-based treatments caused leukemia in volunteers, the

approach has recently produced what appear to be its first cures.

More than a dozen children born with genetically defective immune

systems are now living normal lives because of injections of new

genes.

A Targeted Genetics spokeswoman declined to comment on the autopsy

findings, saying the company will make a full presentation at a

National Institutes of Health meeting on Sept. 17.