http://www.organtx.org/tx/isletcell.htm
Transplant Breakthrough May Lead to Potential Diabetes Cure!
Satellite Feed 5-13-03 Subject: Interventional Radiology Technique
Provides Safe Reliable Transplantation of Insulin Producing Islet
Cells Into the Liver Without Surgery; First of Three Cutting Edge
Medical Feeds in May NEW YORK, /PRNewswire/ -Source: Society of
Interventional Radiology- A new clinical trial shows unstable Type-1
diabetics can stop regular insulin shots and become insulin free
after islet cells are transplanted into their liver.
The Society of Interventional Radiology reports that one year after
undergoing an islet cell transplant, 81 percent of the patients are
insulin free. This is a major medical advancement that could lead to
helping the 1 million Americans who suffer from Type-1 diabetes, the
condition in which the body produces no insulin which is necessary
for the body to use sugar-the basic fuel for the body's cells.
Interventional radiology allows the cells to be placed directly in
the liver without surgery, where they can begin producing insulin
almost immediately. The study shows that the interventional radiology
delivery technique provides reliable and safe access to the liver,
and together with islet cell separation techniques and
immunosuppressive treatment, offers a significant development in the
treatment of Type-1 diabetes.
During the two-hour minimally invasive procedure patients are awake
and can watch the procedure on a monitor. Because of this non-
surgical technique, recovery is rapid and patients can go home the
next day. The feed includes bites with transplant team doctors and a
Type-1 diabetic of 23 years who's been insulin free for one year
after two islet transplants, as well as b-roll footage of the
hospital, the patient and the interventional radiology suite. A list
of transplant centers for patients is available at www.SIRweb.org on
the homepage under "Hot Topics."
Two additional cutting edge medical stories focus on: Minimally
invasive laser treatment of varicose veins which affect half of all
people 50 and older. Fertility results after non-surgical treatment
of uterine fibroids (UFE) that affect up to 40 percent of all women
35 and older and result in 200,000 hysterectomies each year. These
topics feed on May 20th (1:30-2:00 PM ET) and 21st (10:30 - 11:00 AM
ET) with the same satellite coordinates as the above mentioned
project.
These feeds are provided by the Society of Interventional Radiology
(SIR) for your free and unrestricted use. Interventional Radiologists
are board certified doctors who specialize in minimally invasive,
targeted treatments performed using imaging guidance. They use their
expertise in reading x-rays, ultrasound, MRI, and other diagnostic
imaging, to guide tiny instruments such as catheters, through blood
vessels or the skin to treat diseases without surgery.
Promising Results for Islet Cell Transplantation to Treat Diabetes
May Lead to Potential Cure - Interventional Radiology Technique
Provides Safe and Reliable Delivery of Cells to the Liver Without
Surgery - SALT LAKE CITY 3-28-03 /PRNewswire/ -- Early data shows
that transplanting healthy, insulin producing islet cells by infusion
into the portal vein to the liver enables uncontrolled type 1
diabetic patients to become insulin free, according to data presented
here today at the 28th Annual Scientific Meeting of the Society of
Interventional Radiology. "This work is the collaborative effort of
transplant specialists and interventional radiologists. This early
data shows that if we can get enough healthy islet cells to the
liver, diabetes patients could potentially be cured," says Richard
Owen, M.D., interventional radiologist at the Alberta Hospital. The
islet cells become rapidly engrafted into the liver and secrete
insulin almost immediately. The study shows that the interventional
radiology delivery technique provides reliable and safe access to the
liver, and together with islet cell separation techniques and
immunosuppressive treatment, offers a significant development in the
treatment of type 1 diabetes.
Interventional radiologists specialize in performing minimally-
invasive treatments using guided imaging to treat diseases without
surgery. Using ultrasound or fluoroscopic guidance, a needle is
placed through the skin to a branch of the right portal vein, where
the cells are infused. "Interventional radiology allows the cells to
be placed directly where they need to engraft to begin producing
insulin for the patient. This minimally invasive technique is a safe,
accurate and practical means of delivery in the hands of a skilled
interventional radiologist," says Dr. Owen, in his scientific
presentation New Frontiers in Interventional Radiology. The portal
vein is the site of islet implantation because of the ease of
technical access combined with cumulative data indicating that this
route is the safest and most durable route for transplantation. The
procedure is well within the capability of all interventional
radiologists, and with adequate cell separation and purification, the
procedure and clinical results of this study should be reproducible.
About The Study and Islet Cell Transplantation: Forty-eight patients
had 90 transhepatic portal vein islet cell transplantation procedures
for type 1 diabetes. Twenty-two patients had two transplants, 10
patients had three transplants, and sixteen patients had a single
transplant. In most cases, more than one transplant is required to
obtain a sufficient number of islets to become insulin independent.
On average, only about 5,000 islet equivalents per kilogram can be
obtained from one donor pancreas. Successful islet cell infusion was
achieved in all cases by the interventional radiologist. All of the
patients who received more than 9000 islet equivalents per kilogram
became insulin independent. One year later, twenty-one of the twenty-
six patients that have received the full number of islets (81
percent) are insulin free. Most importantly, they are now
metabolically stable.
"The people who took part in this trial had labile diabetes, which is
dangerously unstable metabolic control. They could no longer tell
when they had dangerous lows in blood sugar and had to test
continuously. These patients were losing consciousness off and on,
were at risk for diabetic coma, and were afraid to go to sleep at
night, for fear that they would not wake up. Islet transplantation
has given them their lives back," says Owen.
Treatment Availability: This is a very active area of research and
the Alberta hospital in Edmonton, Canada is one of several hospitals
in the United States and Canada with islet cell transplantation
programs. Although not yet available outside of a clinical trial,
multi-national trials using the Edmonton protocol are now in
progress. This treatment is still being studied and is reserved for
diabetics who have unstable diabetes to such an extent that the risks
of transplantation are considered less than the risk of uncontrolled
diabetes.
Recent developments in tailored immunosuppression for islet
transplant recipients, combined with the delivery of sufficient
islets, has led to rejuvenated enthusiasm for clinical islet
transplantation as a potential therapeutic option for selected
patients with type 1 diabetes. This enthusiasm is based on current
insulin independence rates at one year exceeding 80 percent, combined
with the minimal morbidity of the interventional approach for
implantation. Improved safety, avoidance of major surgery, rapid
hospital discharge and return to normal activity has been a major
advantage of this approach, making the procedure attractive to
patients.
These new success rates are very encouraging. Prior to these recent
developments, the previous success rates were about 7 to 14 percent.
There are still limitations to the procedure. Isolating the cells
from a donor remains a highly technical and labor intensive process.
If a large enough number of islets can be isolated then they are
transplanted. This early work shows that if we can get enough healthy
islet cells to the liver, diabetic patients could potentially be
cured of their need for insulin.
About the Society of Interventional Radiology: An estimated 5,000
people are attending the Society of Interventional Radiology 28th
Annual Scientific Meeting in Salt Lake City. The Society represents
interventional radiologists -- physicians who specialize in minimally
invasive, targeted treatments performed using guided imaging.
Interventional radiology procedures are a major advance in medicine
that do not require large incisions -- only a nick in the skin about
the size of a pencil tip -- and offer less risk, less pain and
shorter recovery times compared to surgery. Interventional
radiologists pioneered modern medicine with the invention of
angioplasty, the first catheter-delivered stent and the coronary
angiography technique most used worldwide -- state of the art
treatments that are commonplace in medicine today. More information
can be found at www.SIRweb.org SOURCE Society of Interventional
Radiology
Emory performs Georgia's first islet cell transplant 3-25-03 The
Telegraph, Macon - Emory University has performed the state's first
islet cell transplant procedure, which can help end diabetics'
dependence on insulin shots to control blood sugar.
Wendy Kenny, a 42-year-old Covington pharmacist, received the
procedure Thursday. Kenny was diagnosed with type 1 diabetes at age
9. Type 1 diabetes usually occurs early in life. People with the
condition are unable to manufacture their own insulin because their
pancreatic islets don't function.
In the procedure, islets that can restore normal insulin production
are harvested from a donor pancreas and injected through a small
incision in the liver of the recipient. Emory officials hope to do
three or four transplants under the clinical trial that included
Kenny's procedure and possibly another 10 transplants in the future.
Pancreatic Islet Transplantation Produced Insulin Independence In
Type I Diabetics -- A DGReview of :"Achievement of insulin
independence in three consecutive type-1 diabetic patients via
pancreatic islet transplantation using islets isolated at a remote
islet isolation center." Transplantation 1/10/03 by Mark Greener -
Early data demonstrate that pancreatic islet transplantation produces
insulin independence in patients with type-1 diabetes.
Researchers from Baylor College of Medicine, Houston, Texas, United
States, performed pancreatic islet transplantation in three patients
with type 1 diabetes. They also had histories of severe hypoglycaemia
and metabolic instability. Islet isolation, at a site distant from
the transplantation centre, began within 6.5 hours.
All three patients attained sustained insulin independence after
transplantation of between 395,567 and 563,206 pancreatic islet
equivalents (IEQ). Two patients underwent a second islet transplant
with 326,720 and 768,132 IEQ to increase functional pancreatic islet
reserve. Follow-up was between 0.5 and 4 months.
Mean glycosylated haemoglobin values and the mean amplitude of
glycaemic excursions declined in two and three patients respectively.
Islet allografts responded to in vitro glucose stimulus before and
after shipment to the transplant centre. No patient experienced
hyperglycaemic or hypoglycaemic episodes since the transplant. No
complications occurred.
The authors came to three conclusions: first, pancreatic islets
remain viable after shipment to remote sites for transplantation;
second, a small number of regional units could supply isolated
pancreatic islets to remote transplant centres and third, that
pancreatic islet transplantation performed by remote centres can
produce insulin independence.
Transplantation 2002;27:1761-6. "Achievement of insulin independence
in three consecutive type-1 diabetic patients via pancreatic islet
transplantation using islets isolated at a remote islet isolation
center."
15 Million Clinical Center for Islet Transplantation Launched by the
Juvenile Diabetes Research Foundation at University of Alberta - New
Center Expands Promising Edmonton Protocol Research - NEW YORK 11-8-
01 /PRNewswire/ -- The Juvenile Diabetes Research Foundation
International (JDRF) announced today a $15 million grant to open a
clinical center at the University of Alberta, designed to study the
treatment of juvenile diabetes (also known as Type 1 diabetes)
through islet transplantation. The five-year grant is intended to
sustain research into furthering the historic advances of the
Edmonton Protocol diabetes research. The grant was announced at a
JDRF fundraising gala this evening in Toronto, Canada.
The Edmonton Protocol identified islet transplantation as a promising
area of research. It established a set of procedures for islet
transplantation from donor pancreases that can restore normal insulin
production in people with Type 1 diabetes. There are still several
problems associated with islet transplantation and the Center aims to
conduct various research initiatives to address these issues.
"The Edmonton Protocol was a major breakthrough in the path to
finding a cure for diabetes-a disease which affects more than 16
million Americans and 120 million people worldwide. We hope that the
development of this new clinical center will enable JDRF-funded
researchers to make even further strides in understanding how islets
can be used to cure Type 1 diabetes," said Charles J. Queenan III,
Chair of Research for JDRF. "JDRF has long been at the forefront of
funding cutting-edge diabetes research and our goal is to quickly
move more research results into clinical applications."
Overcoming limitations of the Edmonton Protocol - The challenges
associated with the Edmonton Protocol will be paramount to the
research conducted at the Center. These include the fact that two
donor pancreases are required to transplant one patient and there are
relatively few pancreases available. Secondly, it is still difficult
to extract islets from the donated pancreas in a way that makes them
pure enough for transplantation.
Thirdly, researchers cannot distinguish well between high quality
islets, which are very likely to survive transplantation, and low
quality islets, which are not. Finally, researchers need to find a
way to overcome "allograft rejection," the body's normal defenses
that turn on against foreign tissues whenever any kind of transplant
takes place. The Center will accomplish this by testing safer and
more effective immunosuppressive drugs.
"The Edmonton Protocol helped us to understand how we can use islets
to treat people with Type 1 diabetes," says James Shapiro, MD, PhD,
Director of JDRF Clinical Center, University of Alberta. "Now we need
to concentrate on how to alleviate the problems still associated with
this procedure. We are confident that with the support of this new
Center, we will be able to put an increased emphasis on identifying
solutions to these issues."
Clinical Center focus areas - The Juvenile Diabetes Research
Foundation Clinical Center research will begin work immediately. The
new projects that will be undertaken at the Center will include three
focus areas. The first will focus on improving the safety, quality,
and effectiveness of transplanting islets from donor pancreases. The
second is on islet transplants and the complications associated with
diabetes. This study area will examine Edmonton Protocol patients to
determine whether or not the restoration of normal insulin also
reverses the complications associated with diabetes. The third focus
area will look at the quality of life and cost of islet
transplantation. Researchers will investigate how patients feel
before and after transplant and they will also examine economic
evaluations of the transplant procedure.
"These studies are central to further understanding how we can use
islet transplantation to cure people with Type 1 diabetes, and will
help to determine the plausibility and economic realities of the
procedure," says Dr. Shapiro.
Established in 1908, the University of Alberta has grown to be one of
Canada's largest research-intensive universities, with external
research funding in 1999/2000 or more than $213 million (CD). The
University is located in Edmonton, the capital of the province of
Alberta. The University of Alberta serves more than 30,000 students
in 200 undergraduate programs and 170 graduate programs.
JDRF, the world's leading nonprofit, nongovernmental funder of
diabetes research, was founded in 1970 by the parents of children
with juvenile diabetes-a disease which strikes children suddenly,
makes them insulin dependent for life, and carries the constant
threat of devastating complications. Since inception, JDRF has
provided more than $500 million to diabetes research worldwide. In
2001 alone, the Foundation provided $115 million and 87 cents of
every dollar goes directly to research and education about research.
JDRF's mission is constant: to find a cure for diabetes and its
complications through the support of research. For more information,
visit the website at http://www.jdrf.org, or call 800-533-CURE.
SOURCE Juvenile Diabetes Research Foundation Int
l Incara's Catalytic Antioxidant Preserves Human Islets Isolated from
Organ Donors - Data presented to the Cell Transplant Society 10th
Anniversary Meeting RESEARCH TRIANGLE PARK, N.C., Oct. 16
01 /PRNewswire/ -- Incara Pharmaceuticals Corporation (Nasdaq: INCR)
announced that its prototype catalytic antioxidant AEOL 10113
produced an approximate 3-fold increase in the survival of human
pancreatic islets when maintained in culture for up to 6 days with no
loss of beta cell function. Islets are anatomical structures in the
pancreas that contain beta cells, which make and secrete insulin to
regulate blood sugar levels. These data were presented at the Cell
Transplant Society 10th Anniversary Meeting in Keystone, Colorado on
October 16, 2001 by Jon Piganelli, Ph.D. and others from The Diabetes
Institute, University of Pittsburgh, Pittsburgh PA.
"Islet transplantation, a potentially curative treatment for Type 1
diabetes, is limited by the ability to isolate functional human
islets from donors. Currently, islets from two to four organ donors
are needed to perform a transplant into one patient," stated Richard
E. Gammans, Ph.D., MSM, Senior Vice President of Antioxidant
Therapies at Incara. "An agent that can significantly increase the
number of functional human islets available for transplantation would
represent an important advance in islet transplant treatment. These
data also suggest other applications of our catalytic antioxidant
compounds in the management of diabetes and in tissue and organ
transplant therapies."
Type 1 or juvenile diabetes is an autoimmune disease in which the
pancreatic beta cells, which produce and release insulin, are
destroyed. Type 1 diabetics are dependent on daily insulin injections
to stay alive. Onset usually occurs during adolescence or young
adulthood. Diabetic complications int's blood sugar without the need
for daily insulin injections.
"These data suggest a role for our catalytic antioxidants in cell and
organ transplant. In addition to pursuing the effect on human islets,
we are investigating the use of our catalytic antioxidants in our
liver stem cell program," stated Clayton I. Duncan, President and CEO
of Incara. "Our strategy is to leverage our technology platform to
address prevalent metabolic diseases such as diabetes."
Incara Pharmaceuticals Corporation (www.incara.com) is developing
therapies focused on tissue protection, repair and regeneration. This
includes developing a series of catalytic antioxidants for protection
of cells from damage such as that occurring in stroke and cancer
radiation therapy, and also protection of cells from transplant
rejection. Incara is developing liver progenitor cell therapy,
sometimes referred to as adult liver stem cell therapy, for treatment
of liver failure. In addition, Incara is conducting a Phase 2/3
multicenter clinical trial for OP2000, an ultra-low molecular weight
heparin being developed with Elan Corporation for treatment of
ulcerative colitis. Additional background information regarding
Incara's programs is available on the company's website at
www.incara.com.
The statements in this press release that are not purely statements
of historical fact are forward-looking statements, and actual results
might differ materially from those anticipated. These statements and
other statements made elsewhere by the company or its
representatives, which are identified or qualified by words such
as "intends," "likely," "will," "suggests," "expects," "might," "may,"
"believe," "could," "should," "would," "anticipates" or "plans," the
negative of those terms or similar expressions, are based on a number
of assumptions that are subject to risks and uncertainties. Important
factors that could cause results to differ include risks associated
with uncertainties of scientific research, clinical trials, product
development activities and the need to obtain funds for operations.
These and other important risks are described in Incara's reports on
Form 10- K, Form 10-Q and Form 8-K and its registration statements
filed with the Securities and Exchange Commission. Readers are
cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date hereof. The company
assumes no obligation to update the information in this release.
SOURCE Incara Pharmaceuticals Corporation
UT gets $1.7 million for cell transplant diabetes treatment 10-13-01
By Mary Powers powers@..., GoMemphis.com -- The
University of Tennessee Health Science Center received a $1.7 million
federal grant to serve as one of 10 national islet transplant centers
designed to make the experimental diabetes treatment more widely
available.
The money will go to expand laboratory space, staff and logistical
support so Memphis can serve as a regional supplier of the insulin-
producing islet cells. Researchers hope the donor cells will prove
effective at curing diabetes or significantly reducing a patient's
risk of blindness, kidney failure and other disease complications.
The grants were announced Friday as a new era of islet cell
transplantation is poised to begin. The Food and Drug Administration
has approved about 30 islet cell transplant programs nationwide.
Transplants are under way in about a half-dozen.
The UT Health Science Center is home to one of those programs. Dr.
Osama Gaber, UT transplant division chief, said the university has
approval to transplant up to 12 patients. They will likely begin next
year.
Because it costs about $1 million to establish a lab to prepare islet
cells for transplantation, Gaber said the federal grants are designed
to build networks to provide cells for transplantation. Researchers
in Memphis and three other UT campuses are involved in the effort.
The approach is appealing because, unlike treating a patient's
diabetes by replacing the entire pancreas, islet cell transplantation
is an outpatient procedure that requires less suppression of a
person's immune system.
Heme Oxygenase-1 Protects Islet Cells From Destruction Following
Transplant WESTPORT, CT (Reuters Health) Oct 01 01 - Induction of
heme oxygenase-1, a ubiquitous stress protein, protects islet cells
from local inflammation and improves the function of such cells after
transplant in rodents, according to data published in the September
issue of Diabetes.
The findings suggest that "strategies aimed at inducing heme
oxygenase-1 upregulation might result in improved success in islet
transplantation" as a treatment for diabetes in humans, conclude Dr.
Luca Inverardi, of the University of Miami School of Medicine in
Florida, and colleagues there and at Harvard Medical School in
Boston.
The researchers examined the role of heme oxygenase-1 upregulation in
the protection of transplanted islets both in vitro and in mice. They
note that prior studies of this molecule suggested that it has potent
anti-inflammatory properties and could be useful in this setting.
Indeed, heme oxygenase-1 upregulation caused a reduction in
inflammation- or Fas-associated apoptosis in vitro and an improvement
in islet cell function after transplantation in vivo.
"Islet transplants are susceptible not only to the occurrence of
rejection and recurrence of autoimmunity in type 1 diabetes patients,
but also to nonspecific inflammatory events that take place at the
site of implantation, which might contribute significantly to graft
failure," Dr. Inverardi and colleagues note. The ability to reduce
the vulnerability of these cells to local inflammation could have
important implications, they say, for the success of islet cell
transplantation.
Source: Diabetes 2001;50:1983-1991.
Islet transplants offer hope that diabetes can be cured - The
experimental treatment is hailed as a breakthrough. 6-22-01 By Marie
McCullough, INQUIRER STAFF WRITER - The Philadelphia Inquirer -
Robert Teskey began to dread going to sleep as the diabetes that had
defined his life became almost impossible to control, despite maximum
insulin doses. The lawyer from Edmonton, Canada, had to set an alarm
for the middle of the night, check his blood sugar and force himself
to eat something. If he didn't, he might slip into a diabetic coma
and never wake up. Now, two years later, Teskey, 55, is among a tiny
but growing group of Type 1 diabetes patients who appear to have been
cured by experimental transplants of islets, the pancreas cells that
produce insulin.
"After my third transplant, I've never taken another injection of
insulin," said Teskey, who had battled so-called juvenile diabetes
since he was 14. "I can eat whatever I want. And I don't have to eat
all the time." The long-sought breakthrough in treatment, announced
last year by a research team led by James Shapiro at the University
of Alberta in Edmonton, will be a hot topic at the American Diabetes
Association's annual meeting, which gets under way today in
Philadelphia.
Experts stress that transplants are suitable only for a minority of
people with Type 1 diabetes, which is the least common of the two
types of diabetes, afflicting less than 10 percent of all patients.
Still, patients and their families are thrilled by the promise the
new therapy holds. "There's still a lot to be learned, but this is
the most optimistic I've been in 30 years," declared Lee Ducat, the
Philadelphia-area mother who founded the Juvenile Diabetes Foundation
after her son's diagnosis. "To take patients who are terribly ill and
going in and out of shock and give them a normal life . . . this is
an unbelievable result. They say they never knew what feeling normal
is all about."
The "Edmonton protocol," initially tested on Teskey and seven others,
has now been used on 17 Canadian patients. Only two have rejected the
transplants, according to preliminary reports. At least 11 U.S.
patients have been successfully treated at the University of Miami
and a few other institutions. Now, 10 scientific teams - four in
Europe and six in the U.S. - are poised to test the protocol on 40
more patients, using funding from the National Institutes of Health
and the Juvenile Diabetes Foundation. The foundation is also funding
trials of slightly different protocols at the University of
Pennsylvania and three other centers. "This is a remarkable advance.
It is very exciting technology," said Penn surgeon Ali Nagi, who has
been studying islets for 30 years.
More than a million Americans and 600,000 Canadians have Type 1
diabetes, sometimes called juvenile diabetes although people of any
age can get it. For unknown reasons, their immune systems destroy
their islets, which secrete insulin, a hormone essential to
converting blood sugar into energy. (In Type 2 diabetes, which is
often linked to obesity, the body doesn't produce enough insulin or
use it adequately.)
Type 1 patients must inject insulin daily and regulate blood sugar by
monitoring diet, exercise and stress. Even so, many ultimately go
blind, develop kidney failure or lose limbs because of circulation
problems. Patients are usually aware of dangerous drops in blood
sugar because of symptoms such as sweating and disorientation. But
those like Teskey become insensitive - "brittle," doctors call it -
to this fluctuation.
Before Edmonton, attempts to fix this metabolic disorder with islet
transplants were disappointing. Still, the new protocol poses both
medical and technical obstacles. While the actual operation is minor -
basically, a transfusion - patients must take immune-suppressing
drugs indefinitely to prevent their bodies from rejecting or
destroying the islets. The drugs cause side-effects such as mouth
sores, and put patients at risk of infection and illness.
That's why transplants are currently considered only for "brittle"
patients and those who need a kidney transplant, which also requires
immune suppression. "We need to be able to do this [transplant]
without long-term immunosuppressants," said Hugh Auchincloss, who is
leading a transplant trial and heads the Juvenile Diabetes Foundation
Center for Islet Transplantation at Harvard Medical School. "There
are 57 ways to do it in mice, but none yet in humans. And to be
honest, we don't see a clear answer at this point."
Another problem: Islet cells are scarce (only 2 percent of all cells
in the pancreas) and difficult to obtain from donated cadaver
pancreases, the current source. Researchers are trying to develop
other sources such as genetically engineered liver cells, stem cells,
or pig pancreases. The Edmonton protocol "was a big step forward, but
we still have a long way to go to cure diabetes," Auchincloss said.
Pancreas Islet Allotransplantation Maintained With Two Weeks Of
Immunosuppression June 4, 2001 WESTPORT (Reuters Health) -
Researchers have for the first time succeeded in transplanting and
maintaining isolated pancreas islet cells into diabetic rhesus
monkeys without long-term sustained immunosuppressive therapy,
according to a report in the June issue of Diabetes.
Dr. Francis T. Thomas, of the University of Alabama at Birmingham,
and colleagues induced diabetes in 11 rhesus macaques with
intravenous streptozotocin. Islet cell donors were selected to have
multiple donor major histocompatibility complex mismatches with the
diabetic recipients.
For immunosuppression, "we used a new drug we developed which wipes
out the CD3-epsilon receptor of T cells, including most importantly
the T cells in the sessile compartments, such as the lymph nodes and
spleen," Dr. Thomas told Reuters Health. The research team also used
15-deoxyspergualin (DSG) after discovering that it blocks maturation
of dendritic cells that present foreign antigens to T cells, Dr.
Thomas said.
A 2-week tolerance induction protocol was initiated on the day of
transplantation. Three protocols were used, anti-CD3 or DSG, or both.
The macaques also received methylprednisolone on days 0 to 2. Within
3 days after the transplant, the recipients exhibited normal
nonfasting blood glucose levels in the absence of exogenous insulin,
the investigators report. All seven animals that received the
combination tolerance induction protocol maintained prolonged graft
survival, four for more than a year. The remaining four macaques
failed to become long-term survivors.
None of the recipients exhibited IgG- or IgM-positive flow cytometry
antidonor crossmatches, although long-term survivors were
immunocompetent with respect to a microbial antigen. Between 6 months
and a year after transplantation, peripheral and total T-cell counts
recovered to their pretransplant levels. T-cell amplification was
limited, as seen by a lower response to an antigen to which the donor
were previously unexposed, Dr. Thomas' group notes. The investigators
also observed "prominent and sustained expression" of interleukin-4
and -10, and normal levels of gamma-interferon. These latter findings
indicate downregulation of peripheral T-helper-2 responses, the
investigators write. This suggests, they add, that "an
immunoregulatory rather than a deletional process underlies this
operational tolerance model."
Dr. Thomas noted that the islet transplantation procedure does not
require hospitalization, and can be done in a radiology department
using duplex Doppler to image the portal vein, into which the cells
are injected. "The patient then gets off the table and goes home," he
added. Dr. Thomas's group has also demonstrated the potential for
using live donors, having achieved successful transplantation of two
animals from one donor pancreas. He said that they have applied to
the FDA to begin testing the new CD3 immunotoxin in a phase I
clinical trial. Diabetes 2001;50:1227-1236.
Single-Donor Islet Transplantation Provides Insulin Independence -
Transplant 2001 By W. A. Thomasson - Special to DG News - CHICAGO,
IL -- May 15, 2001 -- Researchers reported on the first three
patients with type 1 diabetes in whom an islet-cell graft from a
single donor produced prolonged reversal of their disease. A number
of other diabetic patients have achieved prolonged insulin
independence, but these patients, mostly at the University of
Edmonton, in Edmonton, Canada, required multiple grafts from two or
more donors to achieve this goal. Bernhard Hering, MD, and colleagues
at University of Minnesota in Minneapolis, Minnesota, and University
of California, San Francisco, California, presented their findings at
the Transplant 2001 meeting, in Chicago, Illinois.
In developing their transplantation protocol, Dr. Hering and
colleagues addressed optimization of several different areas-pancreas
preservation, islet processing and testing, timing of islet infusion
and induction immunotherapy. They selected what appeared to be the
optimum technique in each area, and it is not clear which was key to
success, or whether the key is a combination of all. To date,
transplants have been done in three patients with type 1 diabetes who
produced no insulin (no C-peptide) and failed to recognize their
hypoglycemic episodes. The number of cells transferred ranged from
8,200 to 15,200 islet equivalents/kg body weight.
All these patients are now insulin-independent at follow-up times
exceeding 240 days for the first two patients and 180 days for the
third. However, the first patient, who received the fewest cells,
produces less insulin than the other two and has impaired glucose
tolerance not requiring treatment. Hemoglobin A1c, a measure of
glycemic control, is within the normal range for all patients. One
patient developed a generalized rash, and all three patients
developed neutropenia. In one case the neutropenia clearly met the
definition of a serious adverse event and in another it was
borderline. In all cases, however, neutropenia responded quickly to
treatment. There have been no rejection complications. Dr. Hering
noted that the Edmonton protocol has been used successfully in a
large number of patients and is therefore appropriately the basis for
the current multi-center trial. Nevertheless, this paper provides
further evidence that we may be approaching the point where type 1
diabetes will be considered a curable disease, he added.
Islet Autotransplantation Combined With Total Pancreatectomy Shows
Benefits A DGReview of :"Pancreas Resection and Islet
Autotransplantation for End-Stage Chronic Pancreatitis" - Annals of
Surgery 4-5-01 By James Adams
Patients with end-stage chronic pancreatitis who undergo islet
autotransplantation combined with total pancreatectomy show decreased
daily insulin requirements and decreased glycosylated hemoglobin
levels. In most cases, however, patients who undergo the combined
procedure compared remain insulin-dependent, researchers report.
Results come from a study of 24 patients who underwent the combined
procedure conducted by investigators at Leicester General Hospital
and University of Leicester, in Leicester, United Kingdom. Patients
underwent the combined procedure during a 54-month period. Early
complications included duodenal ischemia, a wedge splenic infarct,
partial portal vein thrombosis and splenic thrombosis. Long-term
problems were most often the result of intra-abdominal adhesions.
Four patients developed chronic abdominal pain and remained opiate-
dependent. Eight patients developed short-term insulin independence,
and three developed insulin independence. Overall, insulin
requirements and glycosylated hemoglobin levels decreased
significantly in patients who underwent the combined procedure
compared with those who underwent total pancreatectomy alone. "A
prospective, randomized study is therefore needed to assess the long-
term benefit of total pancreatectomy and islet autotransplantation on
diabetic complications," the investigators conclude.
Ann Surg 2001; 233: 423-431. "Pancreas Resection and Islet
Autotransplantation for End-Stage Chronic Pancreatitis"
Islet Cell Transplantation Showing 'Long-term' Results WESTPORT
(Reuters Health) Apr 03 01 - A total of 15 patients with unstable
diabetes have undergone islet cell transplantation at the University
of Alberta in Edmonton in the past few years. All became insulin-
independent after the procedure and 12 have remained so some for
more than 2 years.
Dr. James Shapiro reported the results of his team's experience at
this year's Experimental Biology 2001 meeting in Orlando this week.
Dr. Shapiro said that islet cell transplantation initially resulted
in all patients becoming insulin-independent. Transplantation
resulted in stable blood glucose levels and the first seven patients
who received transplants "all remain insulin-free," Dr. Shapiro said.
"We've learned a couple of important lessons" from this series of
transplant patients, Dr. Shapiro told Reuters Health in an interview
during the meeting. First, the transplant team found that the
immunosuppressant tacrolimus, which they use post-transplantation,
has an adverse effect on kidney function in the few patients with
poor kidney function at the time of transplantation. Second,
immunosuppression has caused stomatitis and hyperlipidemia that has
been correctable with drug therapy.
"Islet cell transplantation is not for every patient," Dr. Shapiro
said. "It is for those patients with brittle disease who have wide
swings in blood glucose levels." However, in that subpopulation, the
procedure has proven to correct blood glucose levels and maintain
them at stable levels over the long-term, he said. He added that
there is little risk in the procedure. If it does not work, the
patient simply resumes insulin therapy. Dr. Shapiro noted that
advances are being made in other areas of transplantation, where
immunosuppression can be stopped after a finite period of time. He
hopes the same can be true with islet cell transplantation.
Multicenter trials of islet cell transplantation are set to start
soon.
UK charity launches diabetes transplant project By Patricia Reaney
LONDON 1-26-01 (Reuters) - A leading British charity launched a
research project on Friday which it hopes will lead to a cure for
diabetes. Diabetes UK said the programme is based on the work of
British-born Canadian surgeon Dr James Shapiro, who has perfected a
procedure to transplant insulin-producing islet cells into people
with diabetes. So far Shapiro and his team have transplanted islet
cells in 15 patients. Thirteen are now completely off insulin and the
remaining two are taking reduced doses.
"We have every reason to believe we can repeat the success of his
team," Moira Murphy, the director of research at Diabetes UK, told a
news conference. Islets are clusters of cells in the pancreas that
produce insulin, which regulates blood sugar levels. In people with
Type I diabetes their islets have been destroyed by their immune
system.
A woman in Michigan was the first person to undergo the experimental
cell transplant in 1998 when she received islet cells and bone marrow
cells from a deceased, unrelated donor.
Shapiro and his team at the University of Alberta in Edmonton, Canada
refined the islet transplant by using specific anti-rejection drugs
and islet cells from two donors. Diabetes UK will duplicate his
method in seven centres in Britain. "This is not a cure but it is a
major step forward," said Shapiro, who attended the launch.
Diabetes UK said it expects to do the first transplant in the summer
and to complete 10 within the first year of the project. The
transplant involves removing the cells from the donor pancreas,
purifying them and then injecting them into the liver of the patient
using a local anaesthetic and an X-ray imaging machine.
In Canada it has been dubbed a "drive-through transplant" because the
injection only takes 5-10 minutes and most patients are back to their
normal routine within 24 hours. But Shapiro emphasised it is not for
everyone. Only patients who have suffered frequent and dangerous
comas and early damage from diabetes will benefit. But they must take
anti-rejection drugs which carry an increase risk of cancer and
infection.
In Britain 1.4 million people have been diagnosed with diabetes and
an estimated one million more have it and don't know it. Type I
diabetes is the most serious form of the disease with patients
needing insulin injections It accounts for 10-25 percent of cases.
Type 2, or adult onset, is a milder condition that can be treated
with diet, exercise or drugs to stimulate the secretion of insulin.
Diabetes can cause kidney failure, strokes, heart attacks, blindness
and nerve damage. It affects 130 million people worldwide and kills
2.8 million each year. Experts estimate the number of sufferers will
increase to 220 million by the year 2010.