ST. LOUIS: Pigs May Hold Key to Diabetes

[Murray Charters <mcharters@xxxxxxxxxxxxxx>]

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


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