Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse study reveals human X-SCID gene therapy poses substantial cancer risk

27.04.2006
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.

Gina Kirchweger | EurekAlert!
Further information:
http://www.salk.edu

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

Ultrathin device harvests electricity from human motion

24.07.2017 | Power and Electrical Engineering

Scientists announce the quest for high-index materials

24.07.2017 | Materials Sciences

ADIR Project: Lasers Recover Valuable Materials

24.07.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>