[aftermathman]

Summary of today's webcast.

http://messages.finance.yahoo.com/St...60&tof=1&frt=2

Neil.

[vlhperry]

I clicked on your link, and it was for a live webcast. Where do you go from there to read the summary.

A Dumb Brunette,
Vicky

[aftermathman]

I do not know if a review has been issued yet, my link is to a review of the webcast by "interested parties".

I thought any information from this meeting would be of interest, (due to its potential impact on some of our trials, (Neurologix, Ceregene, Oxford Biomedica)) so I posted this review of the webcast by chaps who seem to know their stuff.

All gets a bit medical for me however the consensus seems to be that the patient who died had the illness prior to the trial. There appears to be no evidence implicating the AAV vector although work is still ongoing to confirm this. An informal summary lifted from the same message board is reproduced below:

"(1) This patient had moderate RA. She had prior surgery to correct deformities of both feet, and was getting injections of steroids into her knees despite being on maximal medical regimens to control her symptoms. This suggests to me she had pretty severe symptoms.

(2) She signed the informed consent following discussions with her husband and her physician. She had TWO WEEKS during which time she could have changed her mind about the trial. She chose to stay in the study. I feel certain she did not expect the treatment to do her any harm.

(3) The immediate cause of death is still being investigated and no formal autopsy result was released. However, she died of a consumptive coagulopathy due to a large retroperitoneal hematoma that rapsidly progressed over a matter of days. She was being given massive doses of blood products to try to correct the coagulopathy, but they could not correct it. She developed hepatic failure, and progressive end organ failure. Surgeons evaluated her during her course at University of Chicago but felt there was nothing they could do.

(4) She had a mild infection of some sort just prior to the injection of the AAV into her right knee. Serology taken the day of her injection showed evidence of a low grade Histo antigen in her blood. That does not mean she had Histo, but in the face of a negative blood test two months prior it is something suggestive. The physician who reviewed that information felt she PROBABLY had Histo prior to the second injection.

(5) It is not clear to me what caused the progressive consumptive coagulopathy. Infections can do this. A massive retroperitoneal bleed that becomes progressive can do this. As she bled more and more, attempts to transfuse her essentially put most of the blood products into the hematoma. Her liver began to fail, probably due to hypotension and hypoperfusion. The Histo in her liver (there by histology) might have contributed, but the liver biopsy on presentation to the Univ Chicago did not show massive liver necrosis. Her clinical course deteriorated so quickly there was little they could have done during her last few days at University of Chicago.

(6) Preliminary data from the patients in the Phase I study show that even in the face of the high dose of AAV, you cannot find serologic evidence of expression outside the joint. Her PCR studies are still pending at this time.

My impression based on the preliminary autopsy and review of the information presented today : It will be very hard to link the injection of this AAV to her eventual death. You would have to propose that this somehow predisposed her to a consumptive coagulopathy (possibly due to an infection) and caused the retroperitoneal bleed. It will be unlikely that any extra-articular spread of the AAV (if it occurred) could have further immunosuppressed here. That seemed unlikely to most of the physicians in the room. I'm sure many have an opinion, but most seemed perplexed by the clinical course".


This is not issued from a formal source and if I find a "formal" report I will issue ASAP.

Hope this helps, take care,
Neil.

[aftermathman]

http://www.the-scientist.com/news/home/53593/

The cause of death of a patient in a July gene therapy trial was a massive fungal infection, according to an initial autopsy report presented at the NIH Recombinant DNA Advisory Committee meeting today (September 17). Preliminary evidence suggests that adeno-associated virus (AAV), the vector which delivered the therpay, was not to blame, experts said.

The subject, Jolee Mohr, 36, died from widespread histoplasmosis accompanied by a hematoma that ruptured her organs, according John Hart, a pathologist at the University of Chicago who presented the autopsy results. At the time of her death, she had disseminated histoplasmosis in several organs of her body.

Although it is highly unlikely that AAV was responsible for the infection, further tests looking for presence of the expressed protein are needed to conclusively rule out the possibility, according to speakers at the panel.

"It seems that systemic histoplasmosis was a major contributing event that led to a lot of things that went downhill," Mark Kay, at the Stanford University School of Medicine, told The Scientist. "I don't know how people will spin it, but sounds to me like this was bad result of a medical therapy that probably was unrelated to gene therapy."

Mohr was part of Targeted Genetics' phase I/II clinical trial of tgAAC94, an adeno-associated virus (AAV) vector to treat inflammatory arthritis by inhibiting tumor necrosis factor at joints. Beginning July 2, she reported a fever, nausea and vomiting and was admitted to the hospital seven days later. She was transferred to the University of Chicago Medical Center several days later. A CAT scan revealed a massive retroperitoneal hemorrhage which eventually punctured the lungs and displaced the organs in the abdominal cavity. The FDA halted the trial once the adverse effect had been reported by the clinical trial group. Mohr died on July 24.

Since the death of Jesse Gelsinger, a patient in a gene therapy trial in 1999, the field has been dogged by setbacks.

Carol Kauffman, from the University of Michigan, a speaker on the panel, said that in addition to histoplasmosis, the autopsy also revealed severe sepsis and other symptoms often seen in AIDS patients.

There have been 40 known cases of histoplasmosis in patients undergoing anti-tumor necrosis factor therapy.


Neil.

[paula_w]

Thanks very much Neil!

paula