Type 1 Diabetes -- Advances in Treatments
and in Potential Cure(s) 

(Top Posts - Science - 073107)

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July 30, 2007

Experimental Therapy Reverses Type 1 Diabetes
in Mice

Preparatory work for human trials already under
way, researchers say
  http://healthinfo.johnmuirhealth.com/healthnews/healthday/070730HD606783.htm
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Excerpts:

Researchers have accomplished what might be
a cure of type 1 diabetes -- at least in mice ---
and they're taking the first steps toward a human
trial.

...

Now, a three-drug regimen that not only stops
the destruction of beta cells but also preserves
the function of cells that receive and metabolize
insulin has eliminated type 1 diabetes in labora-
tory mice, said ... director of nonhuman primate
research at the Transplant Research Center,
Beth Israel Deaconess Medical Center in Bos-
ton.

...

"We stopped the progression of automimmunity.
The animals could become normoglycemic,"
meaning they had normal levels of blood sugar,
Koulmanda said.

Another major discovery is that inflammation ap-
pears to play a major role in type 1 diabetes, she
added. In fact, one drug used in the treatment
regimen reduced the inflammation of cells that
metabolize insulin.

"Basically, by blocking inflammation, we were
getting the animals to be insulin-sensitive," Koul-
manda said.

Another drug successfully reduced the auto-
immune destruction of beta cells, but that was
not the key to reversing the disease, she said.
Instead, success was linked to blocking inflam-
matory processes that impair cells' responses
to insulin.

Some of the cells involved in insulin metabolism
were found to be resistant to insulin's effects
-- a common phenomenon seen in much more
common, adult-onset, obesity-linked type 2 dia-
betes, Koulmanda said. "This is the first time
anyone has seen insulin-resistant cells in type 1
diabetes," she noted.

A course of treatment lasting less than four
weeks restored normal blood sugar function in
the test mice. In contrast, mice that did not get
the treatment died during that month-long period.

Based on these promising results, the first work
need to start a human trial of the regimen are
about to begin ... The next step will be tests to
ensure that the regimen is safe for human use.

...

The fact that success was achieved in the mice
trials with a relatively short course of treatment
indicates that, for humans, "one might be able
to use relatively brief periods of treatment to
restore normal function," he said.

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Source:   University of Central Florida
Date:  July 31, 2007

Insulin Grown In Plants Relieves Diabetes
In Mice: Holds Promise For Humans
  http://www.sciencedaily.com/releases/2007/07/070730111638.htm
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Excerpts:

Science Daily — Capsules of insulin produced
in genetically modified lettuce could hold the key
to restoring the body's ability to produce insulin
and help millions of Americans who suffer from
insulin-dependent diabetes, according to Uni-
versity of Central Florida biomedical researchers.

...

Professor Henry Daniell's research team genet-
ically engineered tobacco plants with the insulin
gene and then administered freeze-dried plant
cells to five-week-old diabetic mice as a powder
for eight weeks. By the end of the study, the dia-
betic mice had normal blood and urine sugar
levels, and their cells were producing normal
levels of insulin.

Those results and prior research indicate that
insulin capsules could someday be used to
prevent diabetes before symptoms appear
and treat the disease in its later stages, Daniell
said.

He has since proposed using lettuce instead
of tobacco to produce the insulin because that
crop can be produced cheaply and avoids the
negative stigma associated with tobacco.

...

Insulin typically is given through shots and not
pills so the hormone can go straight into the
bloodstream. In Daniell's method, plant cell
walls made of cellulose initially prevent insulin
from degrading. When the plant cells contain-
ing insulin reach the intestine, bacteria living
there begin to slowly break down the cell walls
and gradually release insulin into the blood-
stream.

...

Though produced in lettuce, the insulin would
be delivered to human patients as a powder
in capsules because the dosage must be
controlled carefully.

If human trials are successful, the impact of
Daniell's research could affect millions of dia-
betics worldwide and dramatically reduce the
costs of fighting a disease that can lead to
heart and kidney diseases and blindness.

...

Daniell's method of growing insulin in plants
is similar to what he used for an earlier study
to produce anthrax vaccine in tobacco. In the
earlier study, which also involved mice, Daniell
showed and the National Institutes of Health
confirmed that enough safe anthrax vaccine to
inoculate everyone in the United States could
be grown inexpensively in only one acre of
tobacco plants.

...

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Source:   Johns Hopkins Medical Institutions
Date:  July 31, 2007

New Technique To 'See' And Protect
Transplants Successful In Diabetic
Animal Model
  http://www.sciencedaily.com/releases/2007/07/070730092608.htm
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Excerpts:

Science Daily — Researchers at Johns Hopkins
have found a way to overcome a major stumbling
block to developing successful insulin-cell trans-
plants for people with type 1 diabetes.

Traditional transplant of the cells, accompanied
by necessary immune-suppressing drugs, has
had highly variable results, from well- to poorly
tolerated.

Part of the problem, the Hopkins researchers
say, is an inability to track the cells--so-called
pancreatic beta cells--once they're inside the
body.

Now a new technique encapsulates the insulin-
producing cells in magnetic capsules, using an
FDA-approved iron compound with an off-label
use, which can be tracked by magnetic reson-
ance imaging (MRI).

The product, tested in swine and diabetic mice,
also simultaneously avoids rejection by the
immune system, likely a major reason for trans-
plant failure.

The work will be published in Nature Medicine.

"We're really excited because we can track
where we put the cells and make sure their
protective housing stays intact and that the
cells don't move. This could solve the mystery
of why current transplantation techniques work
only for so long" ...

Current experimental cell transplantation tech-
niques are done "naked and blind," only lasting
a short period of time ... The unprotected trans-
planted cells are vulnerable to attack by the
recipient's immune system, and researchers
cannot see the cells to figure out why they stop
making insulin after a while.

To address both of these challenges, the re-
search team captured beta cells in tiny porous
capsules made from a mixture of alginate, a
gooey material made from seaweed, and Fer-
idex, a magnetic iron-containing material visible
under MRI.

They then used a machine that oozes droplets
of this mixture to surround and encapsulate
individual islet clusters each containing about
500 to 1,000 insulin-producing beta cells.

Once the cells are encapsulated, the shell
hardens, creating a "magnetocapsule" that
measures less than 1/128 of an inch across.

"They're tiny spheres with nano-scale pores
just big enough too let the good stuff out but
keep the bad from getting in" ... The openings
in the magnetocapsule are so small that the
body's immune system sentinels cannot reach
and attack the transplanted cells.

The team first transplanted magnetocapsules
into the abdomens of mice engineered to de-
velop diabetes. Blood sugar levels in the ani-
mals returned to normal within a week and
stayed that way for more than two months. In
contrast, more than half of untransplanted dia-
betic mice died, and the rest had very high
blood sugar levels.

To mimic human transplantation, the researchers
then implanted magnetocapsules into the livers
of swine with the help of MRI fluoroscopy, spe-
cial reflective screens and a computer monitor
that provide real-time imaging.

The liver was chosen, rather than the usual pan-
creatic home of beta cells, because it contains
many blood vessels that can deliver insulin
quickly to the rest of the body.

...

The pigs underwent MRI and blood tests three
weeks after magnetocapsule transplantation.
MRI showed that the magnetocapsules remained
intact in the liver, and blood tests revealed that
the cells were still secreting insulin at levels con-
sidered functional in people.

"We hope that our magnetocapsules will make
tissue-type matching and immunosuppressive
drugs problems of the past when it comes to
cell-based therapies for type 1 diabetes" ...

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