Medical Device Daily Contributing Writer and MDDs

LONDON – The U.S., Canada and Europe are pooling their mouse knockout programs to accelerate the discovery of the function of human genes. The objective is to create a mutation in 20,000 genes in the mouse genome, allowing researchers to determine the role of each in normal physiology and development, and create disease models.

The project will cost €56.6 million ($71.6 million) over the next five years, of which the European Union will contribute $16.5 million and the U.S. National Institutes of Health (Bethesda, Maryland) $52 million.

This, called the largest collaborative research effort after the Human Genome Project, will enable mouse mutants to be generated by any laboratory in a standardized, low-cost manner. Like the Human Genome Project, all data will be publicly available.

The combined program came together when the NIH launched the Knockout Mouse Project (KOMP) earlier this month, awarding grants of $47.2 million for the generation of knockout mice lines and a $2.5 million grant to pay for a data coordination center. The center, to be run from the Jackson Laboratory (Bar Harbor, Maine), will pull together all other existing mouse sequence databases and track the progress of knockout production.

The Canadian and European arms of the project, the North American Conditional Mouse Mutagenesis Program, NorComm and the European Conditional Mouse Mutagenesis Program, EuComm, have been in operation since October 2005.

Mouse knockouts of around 4,000 genes have been generated worldwide so far, while another collaborative project, the International Gene Trap Consortium, has mutated 8,000 mouse genes. Because of overlap between the two, about 15,000 genes remain to be knocked out.

In addition, not all published knockouts are freely available for research. In advance of setting up KOMP, the NIH has purchased rights to existing knockouts from private companies and pulled together disparate resources in public institutes. The NIH estimates that duplication of effort means that currently a single mouse gene is knocked out an average of 2.5 times. Collaborating across national programs and concentrating NIH grants in a few centers will avoid redundancy, create economies of scale and maximize the efficiency of techniques for generating knockouts.

Colin Fletcher, program director at the U.S. National Human Genome Research Institution, said, “The international projects will exchange information and coordinate their efforts in much the same way that teams from many nations collaborated on the Human Genome Project.”

A steering committee of scientists from the three projects and representatives of the funding agencies will coordinate the work.

The program will use a combination of gene targeting and gene trapping to generate the knockouts. Researchers will harvest embryonic stem cells from four-day old mouse embryos, manipulate them to remove a gene and grow them for several days before injecting them into other mouse embryos and implanting them. The resulting mice have some tissues in which a gene has been knocked out, and it is then necessary to crossbreed them to produce lines of mice in which both copies of the gene are knocked out in all tissues.

Other researchers will be able to obtain the mutated embryonic stem cells to breed their own mice. Initially that will be from the individual organizations that carry out the work, but the NIH intends to set up a central KOMP repository.

The consortium, consisting of the Sanger Institute (Cambridge, UK), Children's Hospital Oakland Research Institute (Oakland, California) and the School of Veterinary Medicine at the University of California at Davis, will be responsible for creating 5,000 gene knockouts.

The Sanger Institute also has received grants from EuComm, and to date has produced mutations in more than 3,000 genes. “Through this funding, we will be able to accelerate the contribution we can make to help researchers worldwide make advances against disease,” said Allen Bradley, director of the Sanger Institute. “Our mission is the use of cutting edge research methods to bring new understanding of normal biology and the role of genes in disease.”

Facet wins spine motion device CE-marking

Facet Solutions (Logan, Utah), a developer of products for the posterior spine motion preservation market, said it received CE-marking for its Anatomic Facet Replacement System (AFRS). The company says the AFRS is the first anatomic facet arthroplasty device designed to provide patients with lumbar spinal stenosis and facet degeneration, a motion preserving alternative to fusion. The company is enrolling in an FDA approved Investigational Device Exemption (IDE) clinical study in the U.S. for the product.

Alan Chervitz, president/CEO of Facet, said that the AFRS “provides an anatomic reconstructive alternative to fusion which is sure to benefit patients who suffer from leg and back pain.”

AFRS implants are designed to utilize conventional pedicle screw fixation. The device is implanted with instrumentation that provides reproducible implant placement, according to Facet. “This beneficial combination of both anatomic design and precision instrumentation makes the AFRS a compelling lumbar spine motion preservation solution by allowing surgeons to provide patients with pain relief, while restoring natural motion and stability at the effected lumbar level.”

Facet has received venture capital from De Novo Ventures, Pequot Ventures, and Spray Venture Partners. The company is FDA-registered and certified to ISO 13485.

Gene link to diabetes raises expectations

Claims that the discovery of a gene could help prevent diabetes may raise unrealistic expectations, warn doctors in a recent issue of the British Medical Journal. Earlier this year, scientists discovered that a variant of the TCF7L2 gene was associated with type 2 diabetes. In subsequent media coverage, they claimed this could lead to a diagnostic test to identify people who carry the variant gene and that people who knew of their extra risk would then be motivated to avoid the lifestyle habits that lead to diabetes. The association is robust, the investigators replicating their finding in three large, independent study populations.

But the claim that this knowledge will lead to a diagnostic test and hence to disease prevention — now routine for such genetic discoveries — may not be true and could mislead the public, write Cecile Janssens and colleagues.

No Comments