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

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 continuin g 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., bo th at the Cancer Research Center in Heidelberg, Germany.


'"/>

Source:Salk Institute


Related biology news :

1. Mouse brain cells rapidly recover after Alzheimers plaques are cleared
2. Mouse brain tumors mimic those in human genetic disorder
3. Research Using Mouse Models Reveals A Novel Key Player In The Initiation Of Colon Cancer
4. Mouse gene shows new mechanism behind cardiac infarction in man
5. Mouse with designer liver has enhanced glucose tolerance, insulin response
6. Agilent Technologies Introduces First Commercial Mouse Microarray for Comparative Genomic Hybridization Research
7. Mouse genome much more complex than expected
8. Mouse study: New muscle-building agent beats all previous ones
9. Mouse to man: The story of chromosomes
10. Mouse mimics chronic leukemia, will aid drug development
11. Mouse study reveals new clues about virulence of 1918 influenza virus
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/31/2016)... R.I. , March 31, 2016  Genomics firm ... of founding CEO, Barrett Bready , M.D., who ... members of the original technical leadership team, including Chief ... President of Product Development, Steve Nurnberg and Vice President ... returned to the company. Dr. Bready served ...
(Date:3/23/2016)... March 23, 2016 ... Sicherheit Gesichts- und Stimmerkennung mit Passwörtern ... (NASDAQ: MESG ), ein führender Anbieter ... Unternehmen mit SpeechPro zusammenarbeitet, um erstmals dessen ... wird die Möglichkeit angeboten, im Rahmen mobiler ...
(Date:3/22/2016)... Ontario , PROVO and ... Newborn Screening Ontario (NSO), which operates the ... for molecular testing, and Tute Genomics and UNIConnect, ... management technology respectively, today announced the launch of a ... next-generation sequencing (NGS) testing panel. NSO ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of commercial spectrophotometers and fluorometers ... the 6000i models are higher end machines that use the more unconventional z-dimension of ... beam from the bottom of the cuvette holder. , FireflySci has developed several ...
(Date:6/23/2016)... 2016 /PRNewswire/ - FACIT has announced the creation ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or "the ... a portfolio of first-in-class WDR5 inhibitors for the ... WDR5 represent an exciting class of therapies, possessing ... for cancer patients. Substantial advances have been achieved ...
(Date:6/23/2016)... 2016  The Biodesign Challenge (BDC), a university competition ... harness living systems and biotechnology, announced its winning teams ... New York City . The ... projects at MoMA,s Celeste Bartos Theater during the daylong ... senior curator of architecture and design, and Suzanne ...
(Date:6/23/2016)... Apellis Pharmaceuticals, Inc. today announced positive ... its complement C3 inhibitor, APL-2. The trials were ... studies designed to assess the safety, tolerability, pharmacokinetics ... healthy adult volunteers. Forty subjects were ... dose (ranging from 45 to 1,440mg) or repeated ...
Breaking Biology Technology: