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Eastern Virginia Medical School and GMP Companies, Inc., have announced
that human trials for the INGAP Peptide have begun in three centers in the
United States. Research with the INGAP Peptide is a novel treatment for
diabetes mellitus that is directed at the basis of the disease by
stimulating the regeneration of insulin-making cells in the pancreas. Islet
cell regeneration is an exciting approach to treating diabetes because it
allows the body to heal itself.

Dr. Aaron I. Vinik, Research Director of the Strelitz Diabetes Institutes
at EVMS, remarks, "Based on the success that we had with our animal
studies, we are very excited that islet cell regeneration research with the
INGAP Peptide has reached the phase of human trials."

Phase I and IIa trials, now begun, will test for the INGAP Peptide's safety
in patients with Type 1 and Type 2 diabetes and seek trends toward efficacy
in those subjects. Single and multiple doses of the peptide will be
administered. Once these trials are successfully completed, Phase IIb and
III trials will investigate the Peptide's efficacy in clinical treatment.

Leading diabetes specialists are conducting the trials. Ralph DeFronzo,
M.D. heads one of the trials at The Texas Diabetes Institute at the
University of Texas, San Antonio. The two other trial leaders and locations
are John B. Buse, M.D., Ph.D. at the Diabetes Care Center at The University
of North Carolina in Durham and Robert E. Ratner, M.D. at MedStar Research
Institute in Washington, D.C.

Dr. Vinik has been researching islet cell regeneration since the early
1980's when he and his colleague at the University of Michigan, Dr.
Lawrence Rosenberg, discovered that they could induce new islet cells to
grow when they wrapped hamster pancreases in saran. They immediately began
to examine how this outcome took place. Though the two scientists were to
move to different medical schools - Dr. Vinik to EVMS and Dr. Rosenberg to
McGill University in Montreal-, they continued their research partnership.
In 1997, Vinik and Rosenberg announced that they had discovered a gene,
named INGAP (Islet Neogenesis Associated Protein), they believe to be
responsible for regenerating the islets that make insulin and other
important hormones in the pancreas.

Eastern Virginia Medical School and McGill University patented the INGAP
gene, and in March of 2000, the two medical schools jointly licensed the
gene to GMP Companies, Inc., a global healthcare company located in
Florida, for pharmaceutical development. GMP Companies began investing
millions of dollars in INGAP research and worked with the Institutes to
meet the FDA guidelines for clinical trial approval.

"We believe that INGAP Peptide has the potential to be an important
approach to the treatment of patients with diabetes mellitus," says Bart
Chernow, M.D., President and CEO of GMP Companies, Inc. "As an
endocrinologist who has seen many patients suffer from diabetes, I am
hopeful that the treatment proves to be safe and efficacious so that we can
help patients."

Dr. Vinik says, "The INGAP Peptide respresents a potentially novel
anti-diabetic therapy directed at the basis of the disease because it
stimulates the growth of insulin-producing cells in the pancreas, rather
than treating the metabolic consequences of diabetes such as high blood

Optimistic about the translation of development of the research with
animals to humans, Dr. Vinik explains, "It is very encouraging that INGAP
in humans appears to be remarkably like that in hamsters, and the
antibodies that we have made to different portions of the hamster INGAP
molecule cross-react very well with INGAP in the human and other species."

He continues, "We have been able to synthesize the gene down to a small
peptide made up of a string of 15 amino acids that is responsible for
inducing new islet production in the pancreas. The simpler the compound
when administered for treatment, the less likely complications will occur
in other areas. In our research with small animals, we experienced no
complications, and we saw a reversal of diabetes when INGAP was
administered at an adequate dose and for a sufficient period of time."

Although researchers were testing for safety, not efficacy, in large
animals, they found that when they administered the INGAP Peptide, it was
not only safe, but it also caused the production of new smaller beta cells
within the islets responsible for secreting insulin. They were encouraged
that when the Peptide was administered in the peritoneal cavity, it went
directly to the pancreas and did not concentrate elsewhere in the body.

Also encouraging is the fact that researchers have the ability to
synthesize as much of the INGAP Peptide as they need for therapeutic
treatment. Humans will be receiving the same Peptide that was administered
to the animals. The ability to create the necessary quantities of the INGAP
Peptide for therapeutic treatment gives scientists a wide potential for
application. This is a marked difference from the islet cell
transplantation approach to treating diabetes that is acutely limited by
the number of islets that become available from donors.

Dr. Vinik explains, "There are only a limited number of pancreases that
become available for islet transplants, and even if all were harvested for
the purposes of islet transplantation, then only a few hundred people with
diabetes would benefit. In contrast, every person with diabetes, even if
they have had diabetes for a long time, has precursor cells in their
pancreases that can be transdifferentiated into islets, and there appears
to be no limit in the capacity."

Researchers believe that islet cell regeneration has the potential for
treating Type 1 and Type 2 diabetes. People with Type 1 diabetes have had
their beta cells destroyed by an autoimmune assault in which the body
recognizes its own beta cells as being foreign. Though the beta cells are
destroyed, other cells within the islets that produce hormones and the
precursor cells appear to survive the assault. In Type 2 diabetes the beta
cells don't function effectively. In both cases, the body harbors precursor
cells in the pancreas that can be turned on to become beta cells with the
administration of INGAP.

"For people with Type 1 diabetes, the good news is that after a person has
had diabetes for many years, the autoimmune process tends to die down. It
seems that the body has to see foreign material to keep the autoimmune
flames alive. When there is sufficient destruction of islets that have been
damaged by the process, then the body no longer recognizes these as foreign
and loses interest in further destruction," says Dr. Vinik.

He continues, "In people with Type 2 diabetes, the beta cells do not
function effectively. It was once thought that people with Type 2 diabetes
are merely resistant to the insulin their bodies produce. It is now known
that people with Type 2 diabetes do not produce the number beta cells that
they need. SDI researchers anticipate that if they can overcome the deficit
in pancreatic insulin secretion, then islet cell regeneration will treat
people with Type 2 as well."

SDI researchers believe that the islets created through the regeneration
approach will be recognized by the body as "self," not foreign, so there
may be no need for the immunosuppression therapy that can cause other
complications. If it turns out that immunosuppression is needed, there are
new therapies being developed that are better tolerated by the body.

Dr. Vinik likens the situation of effectively replacing beta cells faster
than they are destroyed to filling a bucket that has a hole in the bottom.
He says, "Even if there is a hole, as long as one pours faster than the
bucket leaks, the bucket will fill. I believe that the same is true for
producing insulin through islet cell regeneration ? if islets are
regenerated faster than they may be lost, sufficient islets can still be
made to reverse diabetes. The interesting thing is that one needs only
about 2% of the total islet mass to be free of diabetes. Say we were to
stimulate the formation of a reserve mass, then that would be equivalent to
plugging the hole in part. We could always go back to the well if

GMP Companies is working with the Strelitz Diabetes Institutes to develop
INGAP into a pharmaceutical application for diabetes treatment. It is not
yet known what form of therapy this will take. And it is not known whether
treatment will be needed for a defined course of time, as was the case in
studies with small animals, or whether a person will need the INGAP Peptide
therapy at certain intervals to induce the regeneration of beta cells.

Dr. Leon-Paul Georges, Director of the Strelitz Diabetes Institutes and
Chairman of EVMS's Department of Internal Medicine, explains, "Much
research lies ahead, but the most exciting thing is that we are now working
with humans; a goal that Dr. Vinik has been working toward since 1983 when
he first discovered that the pancreas could grow new islets. For years, Dr.
Vinik's research was considered too "avant garde" to attract federal
research support. I've been a believer, and I remain a believer in INGAP's

While GMP Companies works in the pharmaceutical arena, the Diabetes
Institutes Foundation continues to fund SDI research work on the basic
science of islet cell regeneration.

Researchers at the SDI continue to investigate how INGAP turns on the
receptor of the beta cell to produce insulin and what other factors may be
necessary for INGAP to work effectively in allowing the beta cells to
create the insulin. They are also seeking to identify people at risk for
developing diabetes and are looking at who may benefit from the INGAP
Peptide's regeneration of islet cells.

Dr. David Taylor-Fishwick, Director of the Cell Molecular Biology
Laboratory at the SDI, says, "Understanding the process of how INGAP works
to regenerate islet cells is extremely important. It can open up new
possibilities for treatment ? possibly without even using the INGAP
Peptide. We may find an alternate way of going into the beta cell and
turning on insulin production."

He continues, "The more that we know about how INGAP works, the greater our
ability to treat diabetes and to identify risk factors for developing the

Looking to the future, SDI researchers believe that someday basic islet
cell regeneration research may someday allow scientists to be able to
predict and identify susceptible individuals, and then prevent diabetes
from ever occurring.
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