Maybe the critter is made by our own bodies .
www.thecampaign.org/newsupdates/sept01c.htmvng study brings warning of tumors
September 4
Newsday
Efforts to genetically engineer viruses to cure deadly inherited diseases are showing signs of success, along with a new and troubling sign of danger, scientists announced on Sept. 3.
Genetic engineering is seen as a potentially quick, easy and long-lasting treatment -- someday. The technique would involve using a virus as a "vehicle" to insert healthy versions of genes into babies born with genetic handicaps, such as Tay-Sachs disease and dozens of others.
According to molecular biologist Mark Sands, his mouse experiments at Washington University in St. Louis were going beautifully last fall when he got a jolting surprise. Of 59 mice in his experiment, six developed fatal liver tumors after they matured into adults. The treatment used viruses to insert a gene to correct an inherited disease called muccopolysaccharidosis type VII, Sly's syndrome.
"It was a total surprise," Sands said about his discovery of tumors in the treated mice. The finding seriously disrupted human trials that were using the virus, called AAV, across the country. AAV is shorthand for adeno-associated virus, a benign virus known to infect without causing disease.
Detailed reports on Sands' results, the liver tumors and another team's success with genetic engineering in mice appeared yesterday in the journal Gene Therapy.
Sands said that after he notified the Food and Drug Administration of his tumor discovery Dec. 7, the FDA briefly halted experiments in Florida, California and Pennsylvania in which engineered AAV viruses were being used or were about to be used in humans.
Now, despite months of study, it still isn't known how or why the few mice in Sands' experiment developed liver tumors. "The bottom line here is that we discovered them, and they are real," Sands said. But "I'm really stumped by this thing."
The discovery is important because AAV is a favorite "vector," or carrier that scientists use to insert new genes into people and animals. In contrast, another virus used as a gene carrier, the adenovirus, causes the common cold. The adenovirus was blamed for the death of one patient, Jesse Gelsinger, in 1999 in a clinical trial at the University of Pennsylvania. The young man's death threw the field into turmoil and stopped some research for months.
"We're appreciative that Dr. Sands called us, even though he's not involved in any clinical studies" with the AAV virus, said Dr. Philip Noguchi, director of the division of cell and gene therapies at the FDA. "He was obviously very shocked when he found this, and of course every investigator using AAV was notified."
Noguchi said two human trials using AAV were under way and one was about to begin when Sands contacted the FDA. The three trials were put on hold, briefly, while officials and scientists assessed all the data they could find from AAV research.
But "we didn't see anything that relates to the ongoing trials" in humans - which were assessing gene therapy for cystic fibrosis and for hemophilia - "so we released the hold," allowing the trialsa to resume, Noguchi said
The two studies under way in humans are being run by Terrence Flotte at the University of Florida to see if it's safe for people with cystic fibrosis to inhale engineered viruses into their lungs. In the Philadelphia study, Dr. Katherine High is injecting AAV into patients' muscle tissue to see if hemophilia can be corrected via gene therapy.
A third human study, in which engineered AAV would be injected into the liver's portal vein, was about to begin at Stanford University when Sands discovered the mouse tumors.
So far, Sands said, the only mice to get the tumors were in his laboratory at Washington University. No problems were found among the mice in Flotte's laboratory in Florida, where mouse and human experiments were under way. It was Flotte who had supplied the engineered virus for Sands' experiment.
Despite the worry about tumors, the gene therapy experiments in mice were producing promising results. Sands said a normal version of the gene that makes an enzyme, beta-glucuronidase, had been inserted by the virus into mice that exhibit almost all symptoms of Sly's syndrome. The disease - caused by the body's inability to process a certain protein - leads to bone deformities, loss of vision and hearing, mental retardation and death.
The new findings do suggest - if the treatment works in humans - that babies born with the genetic disorder may yet become treatable, saving their lives. It also suggests that about 40 similar "lysosomal storage diseases" caused by nonfunctioning enzymes might eventually become treatable.
Flotte and his colleagues at the University of Florida reported similar success at getting functioning genes into mice.
ng study brings warning of tumors
September 4
Newsday
Efforts to genetically engineer viruses to cure deadly inherited diseases are showing signs of success, along with a new and troubling sign of danger, scientists announced on Sept. 3.
Genetic engineering is seen as a potentially quick, easy and long-lasting treatment -- someday. The technique would involve using a virus as a "vehicle" to insert healthy versions of genes into babies born with genetic handicaps, such as Tay-Sachs disease and dozens of others.
According to molecular biologist Mark Sands, his mouse experiments at Washington University in St. Louis were going beautifully last fall when he got a jolting surprise. Of 59 mice in his experiment, six developed fatal liver tumors after they matured into adults. The treatment used viruses to insert a gene to correct an inherited disease called muccopolysaccharidosis type VII, Sly's syndrome.
"It was a total surprise," Sands said about his discovery of tumors in the treated mice. The finding seriously disrupted human trials that were using the virus, called AAV, across the country. AAV is shorthand for adeno-associated virus, a benign virus known to infect without causing disease.
Detailed reports on Sands' results, the liver tumors and another team's success with genetic engineering in mice appeared yesterday in the journal Gene Therapy.
Sands said that after he notified the Food and Drug Administration of his tumor discovery Dec. 7, the FDA briefly halted experiments in Florida, California and Pennsylvania in which engineered AAV viruses were being used or were about to be used in humans.
Now, despite months of study, it still isn't known how or why the few mice in Sands' experiment developed liver tumors. "The bottom line here is that we discovered them, and they are real," Sands said. But "I'm really stumped by this thing."
The discovery is important because AAV is a favorite "vector," or carrier that scientists use to insert new genes into people and animals. In contrast, another virus used as a gene carrier, the adenovirus, causes the common cold. The adenovirus was blamed for the death of one patient, Jesse Gelsinger, in 1999 in a clinical trial at the University of Pennsylvania. The young man's death threw the field into turmoil and stopped some research for months.
"We're appreciative that Dr. Sands called us, even though he's not involved in any clinical studies" with the AAV virus, said Dr. Philip Noguchi, director of the division of cell and gene therapies at the FDA. "He was obviously very shocked when he found this, and of course every investigator using AAV was notified."
Noguchi said two human trials using AAV were under way and one was about to begin when Sands contacted the FDA. The three trials were put on hold, briefly, while officials and scientists assessed all the data they could find from AAV research.
But "we didn't see anything that relates to the ongoing trials" in humans - which were assessing gene therapy for cystic fibrosis and for hemophilia - "so we released the hold," allowing the trialsa to resume, Noguchi said
The two studies under way in humans are being run by Terrence Flotte at the University of Florida to see if it's safe for people with cystic fibrosis to inhale engineered viruses into their lungs. In the Philadelphia study, Dr. Katherine High is injecting AAV into patients' muscle tissue to see if hemophilia can be corrected via gene therapy.
A third human study, in which engineered AAV would be injected into the liver's portal vein, was about to begin at Stanford University when Sands discovered the mouse tumors.
So far, Sands said, the only mice to get the tumors were in his laboratory at Washington University. No problems were found among the mice in Flotte's laboratory in Florida, where mouse and human experiments were under way. It was Flotte who had supplied the engineered virus for Sands' experiment.
Despite the worry about tumors, the gene therapy experiments in mice were producing promising results. Sands said a normal version of the gene that makes an enzyme, beta-glucuronidase, had been inserted by the virus into mice that exhibit almost all symptoms of Sly's syndrome. The disease - caused by the body's inability to process a certain protein - leads to bone deformities, loss of vision and hearing, mental retardation and death.
The new findings do suggest - if the treatment works in humans - that babies born with the genetic disorder may yet become treatable, saving their lives.
It also suggests that about 40 similar "lysosomal storage diseases" caused by nonfunctioning enzymes might eventually become treatable.
Flotte and his colleagues at the University of Florida reported similar success at getting functioning genes into mice.