[MOL] Gene therapy study stopped following death in trial.... [01221] Medicine On Line

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[MOL] Gene therapy study stopped following death in trial....

NEW YORK, Sep 29 (Reuters Health) -- A US gene therapy study has been stopped following the death of a teenager with liver disease who volunteered to participate in the trial.

An "exaggerated" inflammatory response to the viral vector used to carry the gene into cells could have been involved in the death, according to researchers.

The trial was designed to assess the safety of using a virus to carry genes into the liver cells of patients with metabolic diseases, Dr. James M. Wilson told Reuters Health. Wilson is director of the Institute for Human Gene Therapy at the University of Pennsylvania, where the trial was being conducted.

Each patient in the study was administered increasing single doses of the viral vector, with researchers monitoring safety at each stage of the study. The patient who died had been administered the highest dose planned under the experimental protocol.

Wilson said that he and his colleagues are "still evaluating" the exact cause of the patient's death.

"At this point, all that we really know is that the vector was given and that it led to some inflammation in the liver and that this seemed to contribute to the fact that the patient also had an underlying disease of the liver," Wilson said.

The patient's liver disease, ornithine transcarbamylase deficiency, compromises the ability to breakdown nitrogen, which can result in high ammonia levels in the blood, leading to lethargy, disorientation and eventually coma, Wilson explained.

Inflammation at the site of administration is a known risk factor with adenoviral vectors, the Pennsylvania researcher noted. "For example if you administer it down the airways, there are reports that you can get inflammation in the lung. If you administer it into the brain, for treatment of brain cancer, there are reports that you can get some inflammation there."

"In this particular case what we were watching for very carefully was whether the vector itself would cause any inflammation where we had administered it," he said.

"I suspect, at this point, although we're still trying to understand it, that this patient did have an exaggerated response to the vector in terms of inflammation," Wilson said.

Wilson's group has agreed to allow the Food and Drug Administration to disclose what they do know about the case to other investigators in the field. Although the trial was one of the first to test administration of this vector direct to the liver, other groups are investigating the same vector in the treatment of liver cancers.

"I think that viral vectors are extremely efficient, more than others, at transferring genes. The fact is that we are trying to understand what features of them are good and what are bad. We try to learn as much as we can in animals, but these humans studies are very important in trying to understand that," Wilson told Reuters Health.

"We want this information out so that people can be aware of this and can... consider it when they think about what they're doing," he explained.

"The goal is, we've got to try to understand as much as we can from this tragic situation, as to whether it is possible to predict which patients would be more likely to suffer toxicity than others. That's the challenge," Wilson said.