Imagine
this in the May 22nd 2009…yes 2009 issue of the New York
Times
May
22, 2009
First
Case of Diabetes Reported Since 2006
A
case of diabetes mellitus was reported last month. It is the first case
reported in the United States since 2006, the first since the discovery of the
INGAP treatment and several years after the conclusion of two comprehensive
nationwide diabetes campaigns. One campaign involved using INGAP for Type 1
diabetics and the other for Type 2 diabetics who require insulin shots.
The recent case is remarkable because it is so unusual. The outstanding
success of the campaigns is a result of the steadfast efforts of the
scientific community and private public diabetes funding..
Might
this be a possibility? It just
might happen sooner then we expect?
The
Diabetes Treatment to End Insulin Injections-Too Good to be True?
At
the 2002 ADA Scientific Sessions in San Francisco we had the opportunity to
meet with some of the researchers who reported on their research projects.
One of the projects that caught our attention was a little known study
from Eastern Virginia Medical School. This study focused on the use of a
peptide, which upon injection, caused precursor cells to develop into islet
cells and produce insulin in diabetic animals, in which diabetes was
completely reversed.
We
were granted an interview with one of the chief scientists on the project, Dr.
Aaron Vinik. We met with
Dr. Vinik for over 3 hours and walked away believing that this was too
good to be true! We
continued our research into the project by contacting Dr. Vinik’s associate,
Dr. Lawrence Rosenberg from McGill University in Montreal, GMP, the research
company in charge of the research, and Procter and Gamble who is helping to
finance the research. The more
information we had the more excited we became.
Over
the next few issues of Diabetes in Control.com we will present to you
information that we have accumulated from interviews with the lead
researchers, the GMP companies (research company) and also with P&G
Pharmaceuticals, who is a primary investor in the project.
We
hope you will find it to be as informative and exciting as we did.
We know it is in the early stages, but from the current information,
this could be ---------------
Part 1
THE
CURE FOR DIABETES? Or
Too Good to be True!
How
did it start?
We
met with Dr Lawrence Rosenberg of
McGill University while at a conference in Atlanta and he explained.
“It
really started back in 1922 when a technique using cellophane that comes from
the wrapping of cigarettes packages was used to wrap a liver in the
performance of a 2-stage hepatectomy (liver removal) in a dog.”
Then
in the early 1980’s, Dr. Rosenberg a surgical resident was working on
developing an animal model for studying the development of a condition called
chronic pancreatitis, as part of his PhD thesis.
It was known from the previous research, that partial obstruction of
the pancreas could cause this condition in the dog, so he modified the
procedure by dissecting out the pancreatic duct and directly tying a piece of
cellophane tape around it. This is the same tape that is used around gum
wrappers or cigarette boxes. In fact the cellophane tape came as a reel from
Imperial Tobacco!
Because
of the physical properties of the cellophane, a slow progressive obstruction
ensued (versus simply tying of the duct which would have caused an acute
inflammatory reaction with tissue destruction).
His
primary interest at the time was pancreatic cancer and not diabetes.
He hypothesized that duct cell proliferation in the pancreas was a
precursor to pancreatic cancer, and from the previous dog studies, it was
known that the cellophane technique induced cell proliferation in the
pancreas.
The
animal of choice for the study of pancreatic cancer was (and still is) the
hamster. It was impossible to perform the same surgery on the hamster pancreas
as was performed on the dog because of the small size. So really out of
desperation more than anything else, Dr. Rosenberg wrapped the cellophane tape
(cut to a 1 mm wide thickness) completely around the non-dissected head of the
pancreas. Luckily, it resulted in the same partial obstruction as was created
in the dog.
Serendipitously- they discovered that the cell proliferation, which did ensue,
was actually followed by islet cell neogenesis and new islet formation.
Hence was born the cellophane wrap technique coined “Sarandipity”,
for the induction of islet cell neogenesis- the first step on the twenty year
road to INGAP (Islet Neogenesis Associated Protein).
Using
this animal model, he demonstrated that drug-induced diabetes could be
reversed in hamsters.
In 1985, Dr. Rosenberg went to the University of Michigan to complete a
transplant surgery fellowship and the following year met Dr.
Aaron Vinik, currently Research Director of the Strelitz
Diabetes Institutes (SDI) at EVMS (Eastern Virginia Medical School). Dr.
Rosenberg presented the model and data at one of his research conferences and
Dr. Vinik, who was present, was intrigued enough to want to strike up a
collaboration. Together they would try to sort out how the surgical procedure
induced new islet formation. While in Michigan, they prepared a crude
pancreatic extract, called Ilotropin, that exhibited the ability to stimulate
new islet formation when injected into normal hamsters.
In 1987 Dr. Rosenberg returned to Montreal and in 1990 Arthur Vinik moved to
Norfolk. Nonetheless, they continued their collaboration.
Dr. Rosenberg continued to work on the physiology of ilotropin and on the cell
biology of islet cell neogenesis, while Arthur and a newly assembled team
began to try to isolate from ilotropin (a soup of proteins), the active
component. In the interim, they completed a study to demonstrate that
ilotropin could reverse diabetes in hamsters, much as the cellophane wrap
procedure did.
Finally
in 1997,through concerted collaborative effort, they were able to identify the
INGAP gene, as had been expressed in a novel fashion in the cellophane-wrapped
pancreas, Ultimately the INGAP protein was identified as the responsible agent
for islet neogenesis.
Next
week we will bring you details that answer the question:
Diabetes
In Control.com
THE
CURE FOR DIABETES? Or Too Good to be True!
Part
2
Diabetes and
INGAP
How
would this new treatment affect Type 1and possibly Type 2 diabetes?
The
key organ that is affected in the development of diabetes is the pancreas.
Inside the pancreas there are a small group of cells known as Beta
Cells. These cells are responsible for producing insulin, the hormone that
controls the transfer of glucose into energy.
Without insulin your body cannot store or deliver the energy you need
to survive.
In
Type 1 diabetes, there is an insult on the pancreas that affects the beta
cells’ genetic susceptibility, the development of antibodies, and the viral
assault. There is a progressive destruction of the pancreas’ ability to make
insulin and a reduction of beta cell mass until only about 2% of beta cells
remain, and diabetes develops.
In Type 2 diabetes, a person may start with resistance to the action of
insulin, but over time the capacity to make insulin is lost. Type 2 diabetes
is usually never diagnosed if the pancreas can make enough insulin to
compensate for insulin resistance.
Prospective studies in the United Kingdom have taught us, on the day that a
person is diagnosed with Type 2 diabetes, they probably have been developing
the condition for at least 8 -12 years and possibly have already lost up to
50% of beta cell function and have complications from diabetes. Beta cell loss
continues at approximately 3.5% - 5% per year, often culminating in a loss of
all beta cell function within ten years from diagnosis.
Both Type 1 diabetes and Type 2 diabetes exhibit defective pancreatic beta
cell function. It has therefore been proposed that beta cell regeneration
could potentially be a treatment for people with people with Type 1 and Type 2
diabetes.
There is a curvilinear relationship between how much insulin a person’s
pancreas needs to make depending upon how sensitive the body is. If either the
pancreas does not make enough insulin or the body becomes resistant to its
action, diabetes then develops.
The
objective of most research programs is to take people who have fallen off the
curve and enable them to make more insulin or to help them become more
sensitive to the insulin.
The most well-known research vehicle to make this possible is islet
transplantation. A process fully backed by the American Diabetes Assoc. and
the Juvenile Diabetes Research Foundation. In the past year this process has
been highly publicized by the islet transplantation success of the research
group at the University of Alberta in Edmonton, Canada. They have stated that
they can improve on islet isolation, they can include larger islet doses
immediately after islet isolation, and they can use the appropriate drugs so
that the islets are not rejected.
Can this be a truly successful program for millions hoping for a cure? Through
this process, scientists will harvest the pancreas from a donor. Then, they
will introduce those donor islets into a recipient’s liver, and those islets
will begin making insulin normally. This sounds great, but what’s the
reality of the situation.
There are about 5,000 pancreases that become available each year. 2,500 of
them are already committed. About 2,500 may be available for islet
transplantation. It takes 3–4 pancreases to yield sufficient islets to treat
one person; it can only be done with advanced disease; and, it requires a
lifetime of immunosuppressive treatment with toxic drugs. The immunotherapy
may be worse than insulin and is potentially harmful. 2,500 pancreases divided
by the number of pancreases needed to yield sufficient islets only allows
enough islets to be available each year to treat about 600-700 people. Even if
we double this amount, how do we treat the 1.5 million Type 1 patients –
many of them children? What about
the16 million Type 2 patients in the United States? There needs to be an
alternative approach.
Stem
cell research has been in the news lately, yet with all the sociopolitical
issues, who knows if that will ever be available.
So
what’s the ideal answer?
Regenerating islets from endogenous adult stem cells in one’s own pancreas.
These islets could express the full complement of the hormones that were
needed – insulin and glucagon – so that in a person’s system, blood
sugar could be lowered as well as raised. There would be no need for
immunotherapy, and we could use benign drugs. This approach could treat both
Type 1 and Type 2 diabetes. There would be sufficient insulin production to
combat the diabetes as well as the resistance to insulin. Insulin secretion
would be regulated. The effect would persist beyond the treatment period. The
treatment would not be associated with any toxicity whatsoever. And we would
target only the adult pancreatic stem cells.
Is it possible? It is now
on it’s way to possibly becoming a reality.
In Part one we explained how the research all began, now lets see where
the research is and where it is going.
The
beginning of this new line of research demonstrated that the cellophane
wrapping reversed streptozotocin-induced diabetes in hamsters. From there,
they were able to identify an active protein called “ilotropin”.
Years were then spent working on that protein, trying to isolate it to
its pure form so that they could administer it to animals made diabetic and
later to people with diabetes. The nature of ilotropin eluded the
researchers. So they decided to change the process around.
They decided to look within the pancreas that was growing again for a protein
that was capable of stimulating new growth. A new technology became available
that enabled them “shake the genetic haystack” and watch the needles, or
proteins, drop out. The researchers found the genetic message and then went
after the gene itself. In doing that, they discovered INGAP (Islet
Neogenesis Associated Protein). It was shown that the protein product was
capable of stimulating islet neogenesis and lowering blood glucose levels.
This finding was published in 1997 in the Journal
of Clinical Investigation. The
protein was created by recombinant (molecular biologic) techniques.
Investigations were begun to determine if this new construct could
treat and reverse diabetes in animals.
This recombinant form of INGAP was given to animals made diabetic with
streptozotocin. Several things happened. It stimulated pancreatic duct
proliferation; it turned out to be the major component of ilotropin; and
antibodies to natural INGAP could neutralize its effect. They then looked to
see if INGAP caused the formation of new islets. Low and behold, it did.
After looking for 15 years for the active ingredient, it turned out
that this gene encodes a protein that is buried in the ilotropin
protein mixture and is doing exactly what they wanted it to do.
Their
work with diabetic hamsters revealed that for every log dose increase of
INGAP, there was a progressive reduction in blood glucose concentration. Each
dose that they gave dropped the blood glucose 35 mg/dl translating into about
a 1% drop in blood hemoglobin A1c. and by repeating the process, they were
able to reverse diabetes 30 – 40% of the time.
Investigation ensued to determine if there was a protein fragment that could
successfully duplicate the action of the whole INGAP protein.
They cut up the protein into little pieces and eventually isolated a
smaller protein, actually a peptide made from a string of 15 amino acids that
yielded the same results.
They
synthesized this new INGAP Peptide in vitro and began further testing to see
if the INGAP Peptide would reach its target and stimulate islets in the normal
hamster.
In an attempt to identify the action, Dr. Gary Pittenger and Dr. David
Taylor-Fishwick, directors of the SDI laboratories, produced a synthetic
peptide fragment of the material and gave it intraperitoneally with a
fluorescent tag. They watched where it went in the body. The results were
incredible. The injected material went straight to the pancreas and the ducts,
it didn’t go anywhere else. Nature made them lucky – they were given a
key to lock that is present in the pancreatic cell. No matter where
you put in the INGAP Peptide, the “key” will find the lock and hone in on
it.
Once
the Peptide got to the pancreatic ductal cells, it seemed to stimulate them to
make new islets. This biological activity of INGAP was
deemed capable of stimulating new islets. The answer was had. “INGAP
Peptide goes where it is supposed to go and could reverse
streptozotocin-induced diabetes in hamsters like the whole INGAP protein”.
At
McGill University they moved to investigate if this Peptide could reverse streptozotocin-induced
diabetes in another species. They used the
C57BL/6/bt black mouse. When made
diabetic, this mouse gets inflammation of the pancreas, and the cells look
exactly like a person with Type 1 diabetes. They investigated if increasing
the dose could attain a greater effect. The answer was, yes. In a small study
with eight animals, the animals that received salt water, the diabetes
remained. In the animals that received INGAP Peptide, the diabetes was
reversed.
The next step was to ascertain how the INGAP Peptide reversed diabetes. With
the animals that received saline treatment, the blood glucose remained
elevated. With those that were treated with INGAP Peptide, the blood glucose
started coming down. After the INGAP Peptide was discontinued, the blood
glucose stayed down. This seemed to indicate that INGAP does more than cause
the pancreas to make insulin. INGAP Peptide possibly had a biological effect
that went beyond just making insulin. The Peptide seemed to have a biological
effect to create new cells in the body that make insulin – new cells that
the body recognized as its own.
In
2000 EVMS and McGill licensed the INGAP technology to GMP Companies, Inc. with one
interest in mind - to make INGAP into a drug to treat diabetes. They formed a
relationship to work together to design and conduct studies to test dose,
safety, efficacy, route of administration, and the possibility of human use.
Together they would meet the Food and Drug Administration’s requirements.
The
Companies and People involved in the INGAP program:
Scott
Mohrland, Ph.D.
is
Senior
Vice President, Therapeutics Division for GMP Companies, Inc. As Senior Vice
President he manages and directs the acquisition, development and
commercialization of pharmaceuticals and other therapeutic modalities within
GMP's Therapeutics Division. Prior to joining GMP Companies, Inc., Dr.
Mohrland spent more than 21 years with Pharmacia Corporation (formerly
Pharmacia and Upjohn), most recently as Vice President of Scientific,
Professional and Government Operations.
Dr.
Mohrland shared with us that INGAP fits well within GMP Companies, Inc.'s
mission of Helping Medical Discoveries Help People™ Worldwide.
INGAP
will be able to take advantage of GMP's comprehensive product development
infrastructure”. “GMP's innovative approach reduces the organizational,
administrative and financial burdens on individual business units, freeing
innovators to concentrate on their research activities.” “Using our
"cradle to commercialization" approach we make best efforts to
ensure that every aspect of the process is shepherded by experts in each
functional area, which we believe increases our probability of success.”
GMP
Endotherapeutics, Inc. is the business unit of GMP Companies, Inc. whose
efforts are dedicated to developing treatments for diabetes mellitus. So far
this relationship has worked well as GMP
was instrumental in helping get the Phase
1 / 2a Clinical Study initiated
rapidly.
GMP
has established a collaborative agreement with Procter & Gamble
Pharmaceuticals on the project. (More on Procter & Gamble
Pharmaceuticals’ involvement next week)
“This
is an exciting time for us even though we know it will be a while before we
can answer the many questions that each phase of the research will tell us.”
“What
makes this research so exciting is that we could have answers that will not
only help those with Type 1 diabetes but also those who have Type 2 diabetes
that require daily Insulin injections.”
Part
Three
INSULIN
INJECTIONS, NO MORE! …
STOPPING
THE DIABETES PANDEMIC-PART III
Too
Good To Be True?
“Too
Good to be True”, that’s what most people say when they hear of the INGAP
research. If in science you have a major break-through that people
don’t understand and you cannot explain how and why it does what it does
people will discount it before they buy in. Especially if it goes against some
of the prevailing theories,. This according to Tom Finn VP of Strategic
Planning for P&G Pharmaceuticals, when I asked him, “Is This Too
Good To Be True”
P &
G is well known for their cleaning and health and beauty products but they
have also been in the pharma business for over 20 years. With over $1 billion
in global sales, their marketed drugs include Actonel for osteoporosis and
Asacol for ulcerative colitis. Beyond that, they look for opportunities to
leverage their long standing expertise in endocrinology. So, P& G
set out to find a product that would be considered break-through technology in
the treatment of diabetes.
Over a
year ago, the GMP Companies approached P&G with the INGAP research.
They took a serious look at the research and the more they checked it out, the
more interested they became. INGAP met their goal of being a possible
break-through in the treatment of Type 1 diabetes and for all insulin users.
Eli
Lilly originally had a license agreement for 100 million dollars and they let
it expire. If this research looked so good to P&G, why did Lilly
drop out? There could be many reasons, but from conversations with
GMP and P&G, the simplest answer was that, Lilly did not have the same
information 2 years ago that P&G had when they made their decision to get
involved.
This
was not the first research that P&G had looked at. They had seen a
lot, but none with the potential of INGAP to make a major impact in the field
of diabetes. They wanted something that was unique and not just another
me too treatment. They also didn’t want to go head to head with similar or
existing technology.
P&G
invested 5 million into the INGAP research and another 24 million into the GMP
Companies because they felt it was a good business model.
P&G
has always included licensing and acquisitions as part of their strategy to
bring new products to market. Their appreciation of good relationships
with the academic community led P&G to realize GMP could become a liaison
between Pharma, and places such as McGill University and Eastern Virginia
Medical School to get P&G exposure to new technology.
Just
how committed is P&G to the INGAP research? According to
Mr. Finn, the collaboration with GMP Companies includes joint coordination of
clinical development, manufacturing and commercialization. P&G is
committed to progress INGAP to the market as long as the technology provides
the promise that is expected in terms of both medical and commercial success.
P&G is excited and committed to bringing their resources to make it
happen.
Where
are we now with the research? Phase one which is the crude single dose
safety study has been completed successfully. Now Phase 1/2A is getting
started and that will look at safety issues related to dose, dose duration,
frequency and dose regiment, The question as to the autoimmune response also
has to be dealt with. Then Phase 2B will follow and provide information as to
how you dose it and how frequent. Each phase will build on the
information we get from each prior study. Phase 3 will be a large study
to get the remaining answers.
If
everything goes well, it could be available to patients in the 2nd half of the
decade.
Tom
added “As we progress to making this available we will also be answering the
questions as to how will we help to educate the patient with diabetes.”
“Because
diabetes is a unique disease, which requires the patient to manage their care,
we will need to develop new monitoring and managing techniques. We will
require new protocols, behaviors, training tools and methods to educate not
only the patients but also the medical community. With INGAP in early stage
development, it is too soon to be making specific plans.. But we know that
medical and patient education programs will be necessary and P&G has
the deep expertise and commitment to make it happen when ready..
Besides
having a sales force of more than 1500, they are also very committed to have
the pharmacist be part of the process. P&G feels pharmacists would
be key to the success of a product like INGAP. “Pharmacists are the
front line players, whether it be compliance, side effects, or just knowing
which patients have diabetes. We will be dedicated to a pharmacist program,
which will be a key aspect to the INGAP program.”
As to
the future of INGAP, “at this point in time, we are not comfortable saying
that we might have the cure for diabetes but, we feel that we are looking at a
very exciting therapy with a lot of questions that still need to be answered.
It might provide an insulin holiday rather than a cure, we only can hope and
work diligently to answer the needed questions.”
When
asked about INGAP by those people with diabetes, Tom tells them that we have a
potentially game changing breakthrough product that could ideally eliminate
their need for insulin by growing new fully-functioning islet cells in their
own bodies. But we still have a lot to learn about this new drug and how the
body will respond to it. P&G, GMP and the key investigators are
working hard to generate this learning as fast as possible.
Prior
to INGAP
In 1929
a surgical procedure was used on two juveniles with type 1 diabetes.
They performed surgeries which tied off the tail of the pancreas in both
individuals. In both cases the islets increased in size and
quantity and improved both insulin sensitivity and control. Sixty
years later we find that INGAP might have played a role in the success of the
early surgery. “THE EFFECT OF LIGATING THE TAIL OF THE PANCREAS IN
JUVENILE DIABETES” was published in
Surg
Gynecol Obst 53:45-5 in 1931.
Diabetes
and INGAP: Where do we stand now
According
to Dr. Vinik, the animal studies showed the drug was well tolerated in mice
and dogs. Therefore, it was concluded that it was safe to give animals
and likely to be safe to give to humans. Then, on February 12, 2001, GMP
companies met with the FDA for a preliminary review of the program. In July
the application was received at the FDA and approval given in September.
On December 5, 2001, the human trials began.
Part
one of Phase I/2A, looking at just the safety issues was finished this summer
and Part 2 of Phase 1/2A trials are now beginning and will be conducted in two
stages.
Stage 1
is comprised of administering increasing single doses of INGAP Peptide to 30
insulin deficient patients, both Type 1 and Type 2.
Stage 2
is comprised of 34 days of administration of INGAP Peptide. There are 32
patients in Stage 2.
The
primary objective of these studies is to evaluate the safety and tolerability
of single and multiple doses of intramuscular INGAP Peptide administered for
the first time in humans.
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.
headed 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 Chapel Hill and Robert E. Ratner, M.D. at MedStar Research
Institute in Washington, D.C.
Dr.
Vinik says, “The INGAP Peptide represents 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 sugar.”
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, may have precursor cells in their
pancreases that can be trans-differentiated into islets, and there appears to
be no limit in the capacity.”
These researchers believe that islet cell regeneration has the potential for
treating Type 1 and Type 2 diabetes. People with Type 1 diabetes probably 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 may harbor
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 seems 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 possibly 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 have enough beta cells to produce the
insulin they need. SDI researchers anticipate that if the INGAP peptide 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 necessary.”
GMP Companies is working with the Strelitz Diabetes Institutes(SDI) and
McGill University to develop
INGAP Peptide 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 and Dr. Rosenberg have been working toward since 1983 [it
was 1986 that Dr. Vinik got involved, although the research began at McGill in
1980!] when they first
discovered that the pancreas could grow new islets. For years, Dr.
Vinik’s and Rosenberg’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 potential.”
While GMP Companies and P&G work in the pharmaceutical arena, P&G and
the Diabetes Institutes Foundation continues to fund SDI research work on the
basic science of islet cell regeneration. [P&G
and GMP continue to fund McGill's research effort in this area].
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.
With
Part 2 of Phase 1/2A trials now underway they will be able to begin to answer
many questions that remain:
What
Controls INGAP?
What
are its factors - because they may be able to use these factors to stimulate
an individual’s own production of INGAP?
What
does INGAP control – because somewhere down the line they may find another
molecule that INGAP turns on and then we can use that molecule or a smaller
molecule or even find the receptor – the key to the lock?
Then
there will be the need to establish who INGAP can help.
Who in
the general population has a genetic susceptibility. The methods need to
be developed and acquire the technology to evaluate this.
Who is
deficient in INGAP so that it can be replaced?
A
closer look at Type 1 and Type 2 diabetics, those people who don’t have
insulin and those people who don’t have enough insulin.
Learning
about the antibodies. People with Type 1 diabetes have antibodies that destroy
the islets. There may be other elements that may be required to use with
INGAP.
Will
INGAP be given by itself or in combination with other factors? In order to
make insulin, a pancreatic beta cell requires multiple different signals that
are very carefully coordinated and regulated. Maybe INGAP can stimulate the
formation of islets, but maybe it is going to require a lot of refinement down
the road.
And
then, in Type 2 diabetes, will the new islets created work effectively? Or,
will they function as badly as they did before. If so, can we use INGAP in
combination with insulin sensitizers.
So
where are we now?
We, at
Diabetes in Control, think that it is not beyond the realms of reason to
anticipate that INGAP alone or in combination with other factors, will
certainly help insulin deficient patients, In addition we believe it will
provide a possible cure for certain forms of diabetes in humans.
THE
CURE: TOO Good to be True? Maybe not!
For the
Feature article:
THE
EFFECT OF LIGATING THE TAIL OF THE PANCREAS IN JUVENILE DIABETES, Click
Here
To
Print the complete feature, Click Here
For
information on participation in the INGAP human trials, please call GMP
Companies at 954-745-3537.
To
view the features individually...
Part 1 of this feature,
CLICK
HERE
Part
2 of this feature,
CLICK
HERE
Part
3 of this feature,
CLICK
HERE
For
more information on INGAP and islet regeneration, please visit the Diabetes
Institutes Foundation's website at www.dif.org or contact the Foundation at
difcure@aol.com.
Please
visit http://www.jci.org/cgi/content/full/99/9/2100
to read the entire research article
To review the Abstract please visit http://www.evms.edu/diabetes/ingap_abstract.html
To
review other collaborations between Dr.Vinik and Dr. Rosenberg please visit http://www.evms.edu/diabetes/research-pubs-abstracts2.html
and http://www.evms.edu/diabetes/research-pubs-abstracts1.html
