Jolee Mohr of Illinois fell ill the day after her right knee was injected with trillions of genetically engineered viruses in a voluntary experiment to find out if gene therapy might be a safe way to ease the pain of rheumatoid arthritis. She was dead three weeks later. And it was a horrid death.
The 36-year-old Mohr so swollen by internal bleeding and her failing kidneys that her husband decided against bringing their 5-year-old daughter to say goodbye. The girl wouldn't have recognized her mother.The nationwide experiment in which Mohr was a volunteer has since been halted. Targeted Genetics Corporation of Seattle, the sponsors say no other problems have been reported, and the company believes patients were adequately informed of the treatment's risks.
U.S. health officials are investigating Mohr's death, and the case is expected to be discussed Monday by advisers to the National Institutes of Health (NIH).
There have been more than 800 gene therapy studies involving 5,000 U.S. patients since the NIH approved the nation's first human gene transfer study in 1989. Yet there are no approved therapies despite 17 years of research, and the only major success — a cure for the rare inherited immune disorder known as "bubble boy disease" — came with a high cost: leukemia linked in 2003 to the virus that delivered the treatment.
Still, the 1999 death of Arizona teenager Jesse Gelsinger is the only reported fatality definitively linked with a U.S. gene therapy study, an NIH spokesman said. And Dr. Theodore Friedmann, who once headed the NIH committee that oversees gene therapy experiments, said developments in medicine often come with problems, even death.
Even if gene therapy is found to be the cause of Jolee Mohr's death, Friedmann said, the method remains promising.
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When Dr. Robert Trapp of the Arthritis Center in Springfield told Jolee Mohr about the gene therapy study, she had lived with rheumatoid arthritis for 14 years, her husband said. She kept the pain, stiffness and swelling in her joints under control with medication.
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To enroll in the study, every patient had to have some form of inflammatory arthritis. Jolee Mohr had faith in Trapp, her doctor for seven years, her husband said.
Jolee Mohr thought the experimental treatment might relieve the chronic pain in her right knee, her husband said, though this stage of the study was simply to find out if the treatment was safe.
Jolee Mohr signed a 15-page consent form Feb. 12. "Knowing her, she probably didn't read through it," her husband said.
The form mentioned some scary possibilities. It said that the genetically altered viruses in the study — called tgAAC94 — "could spread to other parts of your body. The risks of this are not known at this time."
"We have seen this type of spread in animal studies when tgAAC94 has been given by injection into the joint," the form said.
Altered viruses can "damage the DNA in the cells of your body by inserting itself into your genes," it went on. "If this happens, it could put you at risk for developing cancer in the future."
And on page 9, it said unknown side effects could result in "pain, discomfort, disability or, in rare circumstances, death."
The study used a virus that can infect cells without causing human disease. In simple terms, the genetically engineered virus is used as a vehicle to carry a new gene into the body. Targeted Genetics hopes the new gene will help the body make a protein that would ease arthritis pain.
Dr. Trapp made a brief note in Mohr's chart after her visit: "Discussed participation in clinical trial. Consent form received and I answered her questions."
Mohr got the first shot of the test drug two weeks later. She was randomly assigned to get the highest dosing level on both injection dates.
By all accounts, everything was fine after the first shot. But she got sick the day after her second injection, vomiting and running a fever.
Jolee Mohr was in respiratory failure, her kidneys were shutting down and she was septic, meaning she was suffering from a life-threatening immune system reaction that can result from infection. She needed a ventilator to help her breathe, and she was put on kidney dialysis. A fungus infection was discovered throughout her body — it did not respond to medication — and Mohr developed a pool of blood in her abdomen that grew to the size of a watermelon, crushing against her spleen and kidney.
Things became so unbearable for her and her family that Mohr was eventually given drugs to sedate her and lifesaving equipment was removed. And she died a day later.
Details about the experiment's other volunteers have not been released by Targeted Genetics.
Trapp, who did not respond to several requests for an interview, enrolled "seven or eight" patients in the gene therapy study, according to his attorney, David Drake. He described Trapp's enrollment procedures only as "standard," and he declined to comment on how much money Trapp's clinic received from Targeted Genetics, fees meant to reimburse costs.
Trapp, 59, has not faced state disciplinary action and his license is active. In 2002, he settled out of court with a patient who sued him for negligence after she developed eye problems known to be a side effect of an arthritis drug he had prescribed.
The investigation into Mohr's death has steep consequences for Targeted Genetics. The company, which employs 70, has no products on the market and several years ago cut workers and several of its programs.
"A very exciting lead product with the possibility to meet significant unmet need could be jeopardized," said CEO H. Stewart Parker when asked what was at stake for the company. "A program we've spent years on, one where there is a tremendous amount of preclinical data supporting it, is under examination."
She said the company believes the study was done with the "highest level" of responsibility and that it followed federal guidelines. She said there's never been any rush to get the study drug tested and on the market.
Parker also noted that key tests have not yet been done that could link Mohr's death to the gene therapy study. A spokesman at the University of Chicago, which is conducting the tests, said they are underway but that several are needed to determine the cause of death.
Targeted Genetics believes Mohr might have died of a fungal infection that could be blamed on anti-arthritis drugs she was taking, Parker said.
Mohr's family asked the University of Chicago to lead the investigation into her death, but the Food and Drug Administration (FDA) is also investigating, spokeswoman Karen Riley said.
"If there are any implications for the safety of other gene therapy trials, we will take whatever actions that may be needed," she said.
Source-Medindia
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