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2006-03-24 00:26:28 UTC
Scientists Hold Out Hope for Diabetes Cure By Ed Edelson
HealthDay Reporter
THURSDAY, March 23 (HealthDay News) -- Three years ago, scientists announced
a new treatment had cured diabetes -- in mice.
But researchers reporting in the March 24 issue of Science say three
separate attempts to replicate that pioneering study have proven only
partially successful.
The results, while not stellar, still leave the cup of hope at least
half-full for people with diabetes, experts say.
In fact, Dr. Denise L. Faustman, the scientist who performed the first
study, contends the cup is still "100 percent full, because the new studies
confirm that it is possible to stop the process by which the immune system
mistakenly destroys insulin-producing islet cells." Islet cells reside in
the pancreas, but are destroyed in the type 1 form of diabetes.
Faustman is director of Massachusetts General Hospitals Immunology
Laboratory. Her group reported in 2003 that a two-phase treatment had
restored islet cell function in mice with a condition similar to human type
1 diabetes, in which the body does not produce insulin.
Type 1 diabetes generally appears early in life and is much more difficult
to treat than obesity-associated type 2 diabetes, in which the body's
insulin production gradually declines.
Plans for a trial to see if type 1 diabetes can be reversed in humans are
well underway at Massachusetts General Hospital, Faustman said, despite the
partial failure of the three subsequent trials in mice.
In the original trial, the diabetic mice were first injected with TNF-alpha,
a naturally occurring protein that stopped the immune system's attack on the
islet cells. That was followed by an injection of spleen cells from healthy
mice, used because they carry proteins that help immune cells to recognize
and ignore normal tissue.
The idea was that the spleen cells would stop the autoimmune attack, giving
transplanted islet cells time to restore insulin production. But, in a
surprising development, no transplants were needed because insulin was
produced by islet cells that suddenly grew on their own in the rodents'
pancreas -- some of them transformed from the injected spleen cells.
Those same steps were taken in the three new studies, reported by
researchers at Washington University School of Medicine, the University of
Chicago and the Joslin Diabetes Center in Boston.
Again, diabetes was cured in some, but not all, of the mice -- four of 22 in
the Washington University trial, seven of 22 in the University of Chicago
trial, and more than half of those in the Boston trial.
What the researchers in all three trials did not see was the transformation
of the injected spleen cells into insulin-producing cells, however.
"We were able to cure mice with established diabetes, [just] not as well as
she did," said Anita S. Chong, an associate professor of surgery and a
member of the University of Chicago research team. "But this second aspect
of her work we were not able to replicate."
The big question now is why insulin production was resumed in just some of
the mice, Chong said. There are two possibilities, she said -- either a
small percentage of insulin-producing cells survived the initial autoimmune
attack and swung back into action when the attack stopped, or new islet
cells were being produced from surviving stem cells.
Either way, the result of the studies opens up a new route for diabetes
therapy, Chong said, showing that "a diabetic mouse, even as an adult, has
an ability to make new insulin-producing cells."
Dr. David M. Nathan, director of the Diabetes Center at Massachusetts
General Hospital, said he's eager to see if the same thing can be done in
humans. A proposal for human trial has been approved, Nathan said, and
researchers are waiting on the development of a highly sensitive assay that
can track immune cells that attack and destroy insulin-producing cells.
"Denise is working feverishly to perfect the assay," Nathan said. "It is
trying to pick out a very small number of a huge population of cells, one in
every 100,000. To try to go from mice to humans is a huge technical problem,
and we cannot start any human studies until we have an assay for those
autoimmune cells."
"We have patients who are coming in every day donating blood for testing,"
Faustman said. Her estimate is that it will take 18 months for the tests and
equipment necessary for a human trial to be ready. The trial will use
injections of a well-known molecule called BCG to try to reverse the immune
system attack, she said.
Meanwhile, she said, "We are actually elated by these studies. For 20 years,
the hope has been that humans can regenerate insulin-producing cells. When
we began this work we were not even allowed to use the word 'regeneration'
in our papers. By 2003, we were able to use the word. These three landmark
papers are extraordinarily important."
HealthDay Reporter
THURSDAY, March 23 (HealthDay News) -- Three years ago, scientists announced
a new treatment had cured diabetes -- in mice.
But researchers reporting in the March 24 issue of Science say three
separate attempts to replicate that pioneering study have proven only
partially successful.
The results, while not stellar, still leave the cup of hope at least
half-full for people with diabetes, experts say.
In fact, Dr. Denise L. Faustman, the scientist who performed the first
study, contends the cup is still "100 percent full, because the new studies
confirm that it is possible to stop the process by which the immune system
mistakenly destroys insulin-producing islet cells." Islet cells reside in
the pancreas, but are destroyed in the type 1 form of diabetes.
Faustman is director of Massachusetts General Hospitals Immunology
Laboratory. Her group reported in 2003 that a two-phase treatment had
restored islet cell function in mice with a condition similar to human type
1 diabetes, in which the body does not produce insulin.
Type 1 diabetes generally appears early in life and is much more difficult
to treat than obesity-associated type 2 diabetes, in which the body's
insulin production gradually declines.
Plans for a trial to see if type 1 diabetes can be reversed in humans are
well underway at Massachusetts General Hospital, Faustman said, despite the
partial failure of the three subsequent trials in mice.
In the original trial, the diabetic mice were first injected with TNF-alpha,
a naturally occurring protein that stopped the immune system's attack on the
islet cells. That was followed by an injection of spleen cells from healthy
mice, used because they carry proteins that help immune cells to recognize
and ignore normal tissue.
The idea was that the spleen cells would stop the autoimmune attack, giving
transplanted islet cells time to restore insulin production. But, in a
surprising development, no transplants were needed because insulin was
produced by islet cells that suddenly grew on their own in the rodents'
pancreas -- some of them transformed from the injected spleen cells.
Those same steps were taken in the three new studies, reported by
researchers at Washington University School of Medicine, the University of
Chicago and the Joslin Diabetes Center in Boston.
Again, diabetes was cured in some, but not all, of the mice -- four of 22 in
the Washington University trial, seven of 22 in the University of Chicago
trial, and more than half of those in the Boston trial.
What the researchers in all three trials did not see was the transformation
of the injected spleen cells into insulin-producing cells, however.
"We were able to cure mice with established diabetes, [just] not as well as
she did," said Anita S. Chong, an associate professor of surgery and a
member of the University of Chicago research team. "But this second aspect
of her work we were not able to replicate."
The big question now is why insulin production was resumed in just some of
the mice, Chong said. There are two possibilities, she said -- either a
small percentage of insulin-producing cells survived the initial autoimmune
attack and swung back into action when the attack stopped, or new islet
cells were being produced from surviving stem cells.
Either way, the result of the studies opens up a new route for diabetes
therapy, Chong said, showing that "a diabetic mouse, even as an adult, has
an ability to make new insulin-producing cells."
Dr. David M. Nathan, director of the Diabetes Center at Massachusetts
General Hospital, said he's eager to see if the same thing can be done in
humans. A proposal for human trial has been approved, Nathan said, and
researchers are waiting on the development of a highly sensitive assay that
can track immune cells that attack and destroy insulin-producing cells.
"Denise is working feverishly to perfect the assay," Nathan said. "It is
trying to pick out a very small number of a huge population of cells, one in
every 100,000. To try to go from mice to humans is a huge technical problem,
and we cannot start any human studies until we have an assay for those
autoimmune cells."
"We have patients who are coming in every day donating blood for testing,"
Faustman said. Her estimate is that it will take 18 months for the tests and
equipment necessary for a human trial to be ready. The trial will use
injections of a well-known molecule called BCG to try to reverse the immune
system attack, she said.
Meanwhile, she said, "We are actually elated by these studies. For 20 years,
the hope has been that humans can regenerate insulin-producing cells. When
we began this work we were not even allowed to use the word 'regeneration'
in our papers. By 2003, we were able to use the word. These three landmark
papers are extraordinarily important."
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