Tetramers

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Tetramers

Postby bromley » Thu Jul 06, 2006 1:15 pm

Seattle in demand on even a molecular level - Tetramers

Widely sought tetramers help diagnose disease.

Thanks to Dr. Jerry Nepom and his gang of scientists at a research facility few people might know by name, Seattle provides much of the world with a spiderlike molecule that has become one of the research community's hottest new tools.

Tetramers are artificial molecules with four arms that can seek out and latch on to specific targets in the blood, a technology with the potential to dramatically improve the diagnoses and treatment of some of the world's most difficult diseases.

"Lately, we've been using them to see if we can improve the anthrax vaccine," said Nepom, director of the Benaroya Research Institute and a world-renowned expert in the field of immunology. His team has built an anthrax tetramer, he said, but they're also working on tetramers for flu, diabetes, tuberculosis, AIDS, multiple sclerosis and many other diseases.

"We can use these to look at anything the immune system attacks," Nepom said. Tetramers, he explained, allow scientists to locate the one-in-a-million key immune system cell that can tell them exactly what is going on in the body when a vaccine stimulates a protective response or when something goes awry.

Without tetramers, for example, the standard way to check if a vaccine is effective is to immunize someone and test the blood later for antibodies. But antibodies represent only half the immune system response and are a fairly generalised response. The other half is called the cellular response, which involves cells known as killer T cells that the body creates to target infected cells or whatever is regarded as a foreign invader.

"Now, we can answer the question of what is the cellular response to the vaccine -- is it working or not?" Nepom said.

Tetramers are in high demand by labs all over the world. Working through the National Institutes of Health in collaboration with Emory University, the Seattle-based researchers are now the leading distributors of this powerful new synthetic molecule.

Their work is cutting-edge, but their workplace, the Benaroya Research Institute, was launched 50 years ago as the Virginia Mason Research Center. Local physicians created it before the University of Washington Medical School became a giant in medical research and well before the beginning of other research leaders in the region, such as the Fred Hutchinson Cancer Research Center.

"Most docs at the time just did research on their own time, paid for out of their own pocket," said Dr. Randy Pillow, 86, a retired physician and one of the early practitioners at Virginia Mason. "It was not too well-organised."

Things have changed in the past half-century. The Virginia Mason Research Center continued to grow and explore new areas. In the 1980s, Nepom came here to focus on the immunology of diabetes. In 2002, the center changed its name to show gratitude to a local family that donated money for a new research building. Today, the Benaroya Research Institute has some 200 researchers focused largely on immunology.

Some of their work is supported by a non-profit organisation created out of tragedy.

When Judi Rising's son, Pat, came down with a deadly autoimmune disorder in the late 1990s, she set out on a nationwide search for experts. The Leavenworth woman was in Bethesda, Md, at the National Institutes of Health, when she read about one "right in my own backyard."

"I hadn't even heard of the place or Jerry," Rising said. "All I knew was there was so little understanding of these autoimmune diseases."

Her son had been diagnosed with an autoimmune bleeding disorder known as idiopathic thrombocytopenia purpura. Its cause is unknown.

Pat "never came out of the hospital," Rising said, and died at age 33, less than two months after first finding blood blisters in the roof of his mouth. To improve knowledge about autoimmune disorders, Judi and Richard Rising, her husband, created a non-profit organisation, Pat's Fund ( www.patsfund.org), that supports Nepom's work and tries to raise awareness about these diseases.

"The Benaroya Research Institute is one of the top autoimmune research organisations in the world," said Rising, now a board member at BRI. "Jerry's work on tetramers could lead to cures."

Nepom is a bit more circumspect. Tetramers are clearly of value as a new diagnostic tool, he said. The molecules are designed to immediately fluoresce -- light up -- when they've found a target in the blood, he explained, allowing for a simple, direct and quantitative identification of the cell or foreign invader of interest. It's a rapid, direct test rather than the current approach, which is indirect and often requires a wait of weeks or more to get results.

"It is a whole new window on the immune system," Nepom said.

And it appears likely that these artificial molecules could also be tailored to serve a therapeutic purpose, he said. The tetramers could be designed to not only identify specific targets, Nepom said, but also to "redirect" or fix the malfunctioning immune system cells in many autoimmune disorders.

"We're looking into this right now for diabetes in mice," he said.

Tetramers are not yet a household word. But if even half of the many potential uses of this artificial molecule pan out, Nepom and his colleagues are going to have to seriously step up production to satisfy world demand. And unlike some in the industry who might wish to financially capitalise on such a breakthrough, the Seattle scientists aren't looking to make big bucks on tetramers.

"The public has already paid for this through NIH research grants," Nepom said.

"We're happy to provide this technology to anyone in the research community who wants to use it."

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