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[IP] Insulin produced in mouse stomachs

Insulin produced in mouse stomachs

New gene therapy approach may treat diabetes

By Maggie Fox

Dec. 7 - Cells in the stomach and intestine might be retrained, using gene
therapy, to produce insulin and treat diabetes, scientists said in a report
published Thursday.

       THEY SAID they had genetically engineered gut cells in mice to
produce human insulin. The genetically engineered mice lived even after
their pancreatic cells, which normally produce insulin, were destroyed, the
researchers said.
       Their report, published in the journal Science, is the second in as
many months to suggest that gene therapy might be used to treat or even cure
diabetes, which affects 16 million people in the United States alone.
       The idea is to replace the insulin produced by pancreatic beta cells
by genetically altering cells that make similar substances in the body. In
type 1, or juvenile, diabetes, the beta cells in the pancreas are destroyed
and in type 2, or adult-onset, diabetes the body is no longer able to use
insulin effectively.
       Tests on human patients are a long way off, said Timothy Kieffer, a
researcher at the University of Alberta in Edmonton, Canada, who helped lead
the study.
       "The approach that we took in this study is clearly not applicable to
treat human patients, so what we need to do now is develop a suitable
delivery system to get into humans," he said.
       Kieffer, Anthony Cheung and colleagues used cells in the gut called K
cells, which are similar to beta cells.

    K cells secrete the hormone GIP, which works with insulin, which in turn
helps the body use fats and glucose effectively.
       "The role of GIP is to tell the pancreatic beta cells that there is
food in the intestine containing glucose," Kieffer said. He said if they
could be made to produce insulin, the body would probably handle it better
than it handles the injected insulin used by diabetics.
       They took K cells from mice and inserted the human insulin gene. They
 injected this new gene into mouse embryos and found when the mice were
born, they produced human insulin in the small intestine and stomach.
       "This insulin protected the mice from developing diabetes," the
researchers wrote. They tested this by destroying the beta cells of the
mice. Normal mice died of diabetes but the genetically engineered mice
       This could be a useful approach for gene therapy for diabetes, the
researchers said.
       "There are many features of the upper gastrointestinal tract that
make it an attractive target for gene therapy," they wrote. It is easy to
get to without surgery, using tools such as endoscopes, so it would be easy
to deliver gene therapy directly to the area.
       Kieffer said it might even be possible to deliver the new genes
orally, in a pill or perhaps using liposomes, little balls of fat, encased
in food or some other carrier.
       And the gut is full of stem cells - the immature master cells that
can give rise to many other types of cells, which are again preferred
targets of gene therapy. Kieffer said if stem cells could be genetically
changed, instead of mature cells, the effects will last much longer.

       Last month, teams at the University of Calgary and Yonsei Medical
School in Seoul used genetic engineering to make mice produce human insulin
in their livers.
       In February, a team at Ariad Pharmaceuticals Inc. said they
genetically engineered mouse muscle cells to produce extra insulin when
"told" to do so by a drug given orally.
       And Canadian researchers reported in August that they had
transplanted pancreatic islet cells into patients to treat their diabetes.
       Kieffer thinks a gene therapy approach may work better than
transplants, because the immune system will attack any transplanted cells.
Thus patients who get transplants have to take immune-suppressing drugs.

         "A potential feature of the gene therapy approach is that by making
another cell in the body take over the production of insulin, we hope this
would ameliorate the requirement for immunosuppression," he said.
       Kieffer, whose work was paid for by the Juvenile Diabetes Research
Foundation, the Heritage Foundation and the Canadian Diabetes Association,
said he and Cheung had formed a company under the auspices of the University
of Alberta, called enGene, to help move the research along.

       ) 2000 Reuters Limited. All rights reserved. Republication or
redistribution of Reuters content is expressly prohibited without the prior
written consent of Reuters.
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