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[IPp] diabetic email newsletter..interesting



----- Original Message ----- From: "Burton, Michael" <email @ redacted> To:
"JDRFWorldwide" <email @ redacted> Sent: Wednesday, March 13, 2002 3:27
PM Subject: JDRF RESEARCH E-NEWSLETTER #17


JDRF RESEARCH E-NEWSLETTER #17 March 13, 2002

The Juvenile Diabetes Research Foundation's Research E-Newsletter is published
twice a month to provide all those interested with the latest information
about research on type 1 diabetes and its complications. Please forward this
report to others who may be interested.  To add your name to the distribution
list, send an e-mail to email @ redacted <mailto:email @ redacted> with "Subscribe
to e-Newsletter" in the subject line and your full name and postal address in
the message portion of the e-mail. If you do not wish to receive future
mailings of this newsletter, please e-mail to email @ redacted
<mailto:email @ redacted> with "unsubscribe" in the subject line.

In this issue:
1. ADULT STEM CELLS IN HUMAN BLOOD REPORTED
2. TRANSFERRING PROTECTION IN ISLET TRANSPLANTATION
3. CONTROLLING PKC IN DIABETIC EYE DISEASE
4. NEW COMPOUND TO BLOCK DIABETES SHOWS EARLY PROMISE
5. RESEARCH ARTICLES POSTED ON JDRF WEB SITE

1. ADULT STEM CELLS IN HUMAN BLOOD REPORTED The New England Journal of
Medicine in its March 7, 2002 issue published a study by researchers at the
M.D. Anderson Cancer Center in Houston suggesting that stem cells from the
blood can regenerate not just the blood supply but various body tissues.  The
study received extensive press coverage including March 7 stories in The New
York Times and The Washington Post.

The researchers looked at tissue samples that had been taken from the skin,
liver, and intestines of patients who had received bone marrow transplants.
(Bone marrow transplants typically contain "adult" blood stem cells - cells
found in children and adults.) They found that in each tissue there were a few
cells that could be traced back to the donor. This suggested that some of the
adult stem cells in the transplanted bone marrow had developed into skin
cells, liver cells, or muscle cells. While this finding is intriguing,
scientists need to investigate the issue further before conclusions can be
drawn about whether such adult stem cells truly have the capacity to give rise
to various types of tissue, including insulin-producing cells. "This would be
exciting news if it turns out to fulfill expectations, but the results are
very preliminary," says Robert Goldstein, M.D., Ph.D., Chief Scientific
Officer of JDRF.  "Until more research is done we need to pursue work on both
adult and embryonic stem cells to see which holds more promise for treating
and curing diseases like diabetes."

Sharing this view, Dr. Helen Blau, a leading Stanford University adult stem
cell researcher quoted in the Times article, says: "Research on embryonic stem
cells is critical to advances in this area." To read the New York Times
article, click below: <http://www.nytimes.com/2002/03/07/science/07STEM.html>

To read the Washington Post article, click below:
<http://www.washingtonpost.com/wp-dyn/articles/A51417-2002Mar6.html>

To read the latest news about stem research from the Coalition for the
Advancement of Medical Research click below:
<http://www.stemcellfunding.org/fastaction/>


2. TRANSFERRING PROTECTION IN ISLET TRANSPLANTATION

Transplanting healthy islets into people with type 1 diabetes poses a double
challenge to scientists:  First, they must overcome the preexisting
autoimmunity, in which the T cells of a person's own immune system destroy the
islets in the pancreas.  Second, they must overcome "alloimmunity," the normal
defenses against foreign tissue that the immune system activates whenever a
transplant takes place, producing cells to kill the foreign intruder.

Massimo Trucco, M.D., as director of the JDRF Center for Gene Therapy
Approaches to Type 1 Diabetes at the Children's Hospital of
Pittsburgh/University of Pittsburgh, has undertaken a project, "Armor Plating
Islets Against Attack from the Immune System," the goal of which is to give
islets the ability to defend themselves against both auto- and alloimmunity.
To do so, the Trucco team has been attempting to express a number of different
protective genes in islets before they are transplanted. Now, in a new study
published in the February 2002 issue of the journal Diabetes, Dr. Trucco
reports success in transferring ("expressing") a protective gene, an enzyme
known as IDO (Idoleamin 2,3-dioxygenase) in pancreatic islets in mice.

Previously, IDO has been known to protect the fetus: As a fetus develops in
the placenta, it expresses genes inherited from the father, producing proteins
that normally would be perceived as foreign and would draw attack from the
mother's immune cells. However, the fetus avoids this kind of attack by making
IDO, which inhibits activation of the mother's immune response in the
immediate area.  IDO does this by a mechanism that inhibits T cells from
proliferating. In this way, the fetus escapes damage without compromising the
mother's immune response in other parts of her body.

Dr. Trucco and his team now show that expressing the IDO gene in pancreatic
islets in mice also protects islets.   It appears that the islets take up the
protective gene (delivered by a harmless virus) and begin producing IDO, a
process that continues after the islets are transplanted into the recipient
mouse. The researchers suggest that introducing the IDO gene into pancreatic
islets provides a shield against 1) the autoimmune process that causes
diabetes and 2) attack from the immune system of the transplant recipient.
This hindering of the immune response would be limited to the area where the
islets were implanted, so the rest of the immune system could function
normally.  Research employing this islet "armor-plating" technique will
progress to larger animals, with human therapy as the ultimate goal. The study
acknowledges JDRF as the funder of this research.

To read the study abstract, click below (full text may be purchased online):

<http://diabetes.diabetesjournals.org/cgi/content/abstract/51/2/356?maxtosho

w=&HITS=10&hits=10&RESULTFORMAT=&searchid=1015944279371_837&stored_search=&F
IRSTINDEX=0&volume=51&firstpage=356&journalcode=diabetes>

To read a description of the Pittsburgh JDRF center, click below:
<http://www.jdf.org/research/centergoal12c.php>


3. CONTROLLING PKC IN DIABETIC EYE DISEASE

One of the most important findings in recent years in the area of diabetic
complications - documented in a number of studies by JDRF-funded
Harvard/Joslin Diabetes Center researcher, George King, MD - is that high
glucose levels can cause the activation of an important regulatory system in
the blood vessel cells called the protein kinase C (PKC) pathways. Elevated
PKC has been associated with excessive, abnormal growth of new blood vessels
in the eye, as well as in the kidney, legs, and heart.  Dr. King and
associates have also demonstrated that PKC activation can enhance the action
of a growth factor called VEGF, characterized as a major factor responsible
for diabetic proliferative retinopathy, the most severe form of this
complication, and a leading cause of blindness in adults with diabetes.

In a new study published in the Proceedings of the National Academy of
Sciences, Dr. King and colleagues (in Boston, Germany, and Japan) offer
further evidence that PKC and VEGF are involved in the development of diabetic
retinopathy.  Animals with increased PKC activation had more excessive blood
vessel growth occurred in their eyes, which corresponds to what happens in
people with diabetes.  Reducing PKC produced less blood vessel growth in the
eye. A potentially important new finding in the study is that a well known
protein, retinoblastoma protein (Rb), may be intricately involved in the PKC
activation process that leads to the uncontrolled vessel growth. "We have
known for some time that Rb proteins have a role in regulating the growth of
tumors," Dr. King said in a Joslin press release. "This is the first time Rb
has been shown to have a role in blood vessel growth in the eye."

The discovery of the protein action, if confirmed by further studies, could
lead to new drugs to inhibit proliferation of blood vessels in the retina,
said Dr. King. It also could lead to new drugs to promote angiogenesis - blood
vessel growth - in organs such as the heart where more vessels are needed to
compensate for blockages.

Dr. King and his associates have been working with a drug that selectively
inhibits PKC production and action. After years of preclinical study, this
inhibitor, which is given orally, is now in Phase 3 human clinical studies
(seeking definitive proof of effectiveness and safety with larger numbers of
patients) to determine if it can delay or prevent the development of
sight-threatening proliferative retinopathy and diabetic macular edema.

Dr. King's current JDRF-funded research project is studying the role of PKC
and VEGF in cardiovascular disease in diabetes.

To read the abstract of the Proceedings of the National Academy of Science
study, click below

<http://www.pnas.org/cgi/search?volume=99&firstpage=721&DOI=&sendit=Search&a

uthor1=&author2=&titleabstract=&fulltext=&fmonth=Jan&fyear=1990&tmonth=Mar&t

year=2002&tocsectionid=all&hits=10&fdatedef=1+January+1990&tdatedef=5+March+
2002>  (full study may be purchased online)

To read the abstract of Dr. King's current JDRF-funded project, click below:
<http://198.65.199.10/cgi-bin/ndCGI.exe/res_new/pgSearch> (enter "K" under
"Last Name" then scroll down to access Dr. King's study)


4. NEW COMPOUND TO BLOCK DIABETES SHOWS EARLY PROMISE

Research e-Newsletter #4 (March 200l) reported on a new strategy developed by
Sophia Casares, Ph.D., of Mt. Sinai School of Medicine (and a past recipient
of JDRF funding), for identifying drugs designed to target, bind to, and
eliminate specific aggressive T cells - known as CD4 T cells - that play a
central role in the initiation of the immune attack on beta cells that results
in type 1 diabetes.  Dr. Casares described the strategy as the "first truly
specific targeting system" for suppressing some, but not all, T cells, thereby
eliminating the autoimmune response without seriously impairing the body's
overall immune defense.

Now, in a new study posted on February 25 on the advance online edition of the
journal Immunology, Dr. Casares and colleagues describe their success in using
a synthetic protein molecule they developed in their laboratory - dubbed DEF -
in preventing the onset of type 1 diabetes in small animal models prone to the
disease, and - in models that are already diabetic - in restoring normal blood
sugar levels.  Ten of 12 mice injected with DEF every five days resisted
diabetes onset for the 4.5 month treatment period, while control mice lost the
ability to produce insulin in most of their islets within the first 10 weeks.
When DEF was interrupted, it took about 15 days for diabetes to develop.  T
cells already in the pancreas were stimulated by DEF to secrete a compound
known as interleukin-10 (IL-10), which, the researchers state, in turn
"down-regulated" the harmful T cells.

In an interview with Reuters Health, Dr. Casares explains, "The DEF molecule
inactivated the CT4 T cells and stopped them from attacking the pancreas...the
mice were protected against diabetes."  She is now working on making molecules
similar to DEF for use in humans.

To read the abstract or study in Nature Immunology, click below and then on
Advance Online Publication to access article index (registration required to
access study or abstract) <http://www.nature.com/ni/>


5. RESEARCH ARTICLES POSTED ON JDRF WEB SITE

Several articles of interest have recently been posted on the JDRF Web site:
To read a special JDRF Research Report on JDRF's Research Task Force III and
its effect on JDRF funding prioritization and management, click below:
<http://www.jdf.org/research/feature/res022702.php>

To read "Islet Transplantation: A JDRF Success Story" highlighting JDRF's
decades-long leadership in this critical area, click below:
<http://www.jdf.org/research/feature/res021302.php>

To read the proceedings report of the JDRF-cosponsored workshop,
"Encapsulation and Immunoprotective Strategies of Islet Cells," held in
Washington, DC, December 6-7, 2001, click below:
<http://www.jdf.org/research/report/encaps1201.pdf>

To read a report on the results of JDRF's most recent research applications
review, click below: <http://www.jdf.org/research/feature/res030602.php>

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