1.Cancer-causing GE Therapies Signal Urgent Need for Diagnostic Tools - GE free NZ
2.Mouse study reveals gene therapy poses substantial cancer risk - Salk Institute

This research shows that the damaging effects of transgenes did not show up in trials with mice lasting several months - a significant part of their life span as mice only live about 18 months. It took long-term studies allowing the mice to live through their natural life span, to show up the cancer- promoting effects.
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1.Cancer-causing GE Therapies Signal Urgent Need for Diagnostic Tools
GE free NZ press release, Wed, 24 May 2006

Animal studies have shown that a form of gene therapy, previously believed to be successful, has actually caused cancer. This indicates that tests evaluating the impact of genetic engineering (GE) techniques on people are essential.

The latest findings show that scientists do not yet understand the full complexities of gene function and regulation and that GE foods as well as medicines may cause unexpected harm.

"New diagnostic tools are urgently needed so that medical professionals can identify whether an illness is being caused by genetic alterations made to food or as part of gene-based therapy," says Claire Bleakley, president of GE Free NZ in food and environment.

The discovery that GE medicines may also cause harm, including creating cancer, is regarded as a call for greater scrutiny of the widely used, but uncontrolled use of GE technology on populations around the world.

A GE drug which was trialled in the UK earlier this year caused horrific responses in the test 'patients' and almost caused the death of a young New Zealander. Yet the drug manufacturers and regulatory authorities have said very little about the drug being a product of genetic engineering.

"Doctors are also being left in the dark about the possible impact of GE foods that may have been consumed. This gap should have been closed years ago, given that government officials are allowing GE food into the food chain," says Mrs. Bleakley. "But shamefully, it has not been closed."

GE medicines are bound by a regulations much stricter than those controlling GE food. "This should be of great concern to the officials and politicians who have allowed GE ingredients into everything from babyfood to tampons," said Ms Bleakley. "It is a scandal only now coming to light that this has taken place without proper testing, tracking or diagnostic tools to limit the long-term harm that genetic engineering technology could be causing."

ENDS

Claire Bleakley (06) 3089842, 027 348 6731 Jon Carapiet 0210 507 681
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2.Mouse study reveals human X-SCID gene therapy poses substantial cancer risk
Salk Institute press release, April 26, 2006 http://www.salk.edu/news/releases/details_20060426.php

- La Jolla, CA - New animal studies conducted at the Salk Institute for Biological Studies show that the only human gene therapy treatment to date considered to be largely successful, is, in fact, riskier than realized.

The Salk researchers, led by Inder Verma, Ph.D., a professor in the Laboratory of Genetics, discovered that the healthy copy, which replaces the defective gene can itself promote cancer development. Their findings appear in this week’s issue of the journal Nature.

Niels-Bjarne R. Woods, Ph.D., a post-doctoral researcher in Inder Verma's team followed mice treated with the IL2RG gene three times longer than any study had ever before, and found that one-third of the animals developed lymphoma later in their life. This is the same gene being given to patients with X-linked severe combined immune deficiency (X-SCID) - commonly known as the "bubble boy" syndrome - in small clinical trials being conducted in France, the United States, the United Kingdom, and Australia.

Although replacement of IL2RG can cure X-SCID, the Salk scientists urge caution in the use of such therapy on the basis of their new findings.

"We were surprised by the strength of the association between IL2RG gene therapy and development of lymphoma," says Woods. "These results suggest that curing X-SCID by replacing IL2RG in the manner it is currently being done puts patients at an increased risk of developing cancer."

Woods adds that the study could explain why one of three children in the French trial developed T-cell leukemia. Two developed the disease because IL2RG inserted itself into the cellular genome next to a known cancer-causing gene and activated it, but the cause of the third cancer case had not been solved.

The French trial is the largest to date to test IL2RG gene therapy, and of the 10 children treated, nine were successfully cured of X-SCID, although cancer was diagnosed in three of the children. Halted for a time, the trial is now continuing on a case-by-case basis, according to Woods.

In the studies leading up to the human clinical studies, mice were studied post-transplant for less than 6 months, which is a traditional research protocol. The Salk research team, however, allowed the mice to live through their natural life span, which is about one-and-a-half years. Mice that developed lymphoma did so at an average of 10 months of age.

In the human gene therapy trials, leukemia did not appear until 2-3 years after treatment, Woods says.

"This indicates that preclinical experimental treatments involving transgenes should include long-term follow-up before entering a clinical trial," says Woods.

But, more fundamentally, the Salk study suggests that replacement of a gene that serves multiple functions in the body may be much more problematic than therapy to replace a gene that serves a single function, says Verma.

"The bottom line here is that if you replace a gene that has multiple effects, you have to know more about its regulation and its ability to affect other genes, and that requires extensive preclinical work and a much more careful analysis," he says.

X-SCID is caused by mutations in IL2RG, which provides instructions for making the common gamma chain protein. This powerful protein, found on the surface of immature blood cells in the bone marrow, works with other proteins to direct the growth and maturation of a number of different immune system cells, including T cells, B cells, and natural killer cells. These immune system cells that kill invading viruses and bacteria, produce antibodies as well as help regulate the entire immune system. Without the common gamma chain, these cells cannot develop normally, and are unable to protect the body.

Researchers who also contributed to this paper include Virginie Bottero, Ph.D., in the Laboratory of Genetics at the Salk Institute, as well as Manfred Schmidt, Ph.D., and Christof von Kalle, Ph.D., both at the Cancer Research Center in Heidelberg, Germany.

The Salk Institute for Biological Studies in La Jolla, California is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health, and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.