Pigs May Hold Key to Diabetes
By Kristen Philipkoski

02:00 AM Feb. 27, 2004 PT

A breakthrough experiment using embryonic pig insulin cells could lead to a new treatment for diabetes.

In a study at Washington University in St. Louis, researchers took pig cells from very young embryos and transplanted
the cells into diabetic rats. The rats, even without drugs to prevent immune rejection, adopted the pig cells as their
own and produced their own insulin.

If the procedure works in humans, it could not only treat but potentially cure diabetes. The rats continued to produce
insulin via the pig cells for the rest of their lives.

"We envision this technology as a means to replace insulin in type 1 diabetic humans using pig insulin -- which works
just fine in humans," said Dr. Marc Hammerman, a professor of renal diseases in medicine at Washington University and
leader of the study, published in the April issue of The American Journal of Physiology -- Endocrinology and
Metabolism.

Until a human insulin drug was made in 1978 by Genentech, diabetes patients routinely injected pig insulin.

But researchers have been trying to do away with daily injections by transplanting insulin-making cells, or islets
(produced by the pancreas), either from animals or humans. The big problem has been immune rejection.

Any organism's immune system will attack foreign cells, even if they're from the same species. For that reason,
Hammerman and his colleagues used two groups of rats: One was given drugs to suppress the immune response while the
other, the control group, was given no drugs.

The researchers figured the control group would reject the pig cells. Hammerman theorizes they did not for several
reasons. First, the cells were extremely young. The entire pancreas was removed just as it was beginning to develop in
the pig embryo, so the cells didn't have time to develop certain proteins that can cause rejection. The researchers
also placed the cells in the lining of the abdomen, called the peritoneal membrane. Veins from the peritoneum empty
directly into the liver, which is how insulin is secreted normally.

"Nobody's ever taken the cells this early, nobody's ever used the whole pancreas and nobody's ever implanted it into
the peritoneal membrane," Hammerman said.

He hopes to test the protocol in primates by the end of this year. If successful, human trials could soon follow.

Researchers have made progress recently in human-to-human islet cell transplantation. Several humans have undergone the
procedure, but they must take up to 18 pills per day to suppress immune rejection.

It's also difficult to find pancreas donors. Of 6,000 annual donor organs, only about 2,000 are viable, according to
Dr. Marc Hurlbert, associate director of researcher at the Juvenile Diabetes Research Foundation. Meanwhile, 1.5
million people have type 1, also called juvenile, diabetes in the United States and 13,000 new cases are diagnosed
every year.

Hurlbert called the new research promising and said he was hopeful it would pan out for humans.

"Before, all pig cells when put into another species' tissue were robustly rejected by the immune system," Hurlbert
said. "In this model, using developing pig pancreas, it appears we can overcome that."

Researchers are trying other methods to avoid rejection as well. At a company called Revivicor (a spinoff of PPL
Therapeutics, which was started by researchers at the Roslin Institute, where Dolly the sheep was cloned), scientists
have developed genetically modified pigs lacking the genes that cause humans to reject the pigs' cells. They could test
cells from the transgenic pigs in humans by the end of the year.

Transplanting animal cells into humans is known as xenotransplantation. Some people oppose xenotransplantation because
they believe it could introduce new, AIDS-like viruses into the human population. The Food and Drug Administration has
established guidelines to try to prevent complications.

In previous studies using pig fetal neurons to try to treat the brains of Parkinson's disease and stroke victims, the
transplants did not introduce retroviruses, Hammerman said. (Unfortunately the studies also didn't help the patients'
symptoms.)

"There's a theoretical risk, and it's one that needs to be considered," Hammerman said, "but I suspect it will not be
the major obstacle that some people envision."

SOURCE: Wired News
http://www.wired.com/news/medtech/0,1286,62454,00.html?tw=wn_tophead_3

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