Download Top Research Highlights

Summer 2013
Top Research Highlights
Advancing Type 1 Diabetes Science
E
investigators in Colorado, Finland,
long study strengthen the link
distinguished researchers from across
and Germany followed children from
between autoantibodies and the risk
the globe to support research for life-
infancy up to age three to detect the
of developing T1D and highlight the
changing treatments and ultimately a
presence of islet autoantibodies. The
importance of prediabetes research
cure for type 1 diabetes (T1D). Our aim
results give scientists the first true
for disease prevention. The results
is to progressively reduce the burden
estimate of when the process of T1D
give scientists the first true estimate of
of the disease on people’s lives until we
may start, as well as the largest dataset
when the onset of T1D may start, and
can achieve a world without T1D. Please
that exists—more than 13,000 children
will help scientists to focus prevention
enjoy reading about some of the ways
were followed and more than 1,000
efforts on groups who are most likely
that we are working tirelessly to make
children developed autoantibodies.
to become insulin dependent.
very day, JDRF leverages the
expertise and innovation of
that happen.
Early Development of T1D Is
Identified
The human immune system
A global team of JDRF-funded
Key point: Findings from a decade-
In the decade-long study, nearly
70 percent of the 585 young children
studied who had two or more
autoantibodies developed T1D within
10 years, while 84 percent of that
comprises complex biological
group developed T1D in 15 years. Of
structures and processes that
the 474 children with a single islet
protect the body against disease. In
autoantibody, 14.5 percent developed
people with T1D, the immune system
T1D within 10 years. The study revealed,
destroys insulin-producing beta
furthermore, that progression of the
cells in the pancreas, leading to a
disease was faster for those who
lifelong dependence on insulin. This
showed the presence of antibodies
autoimmune attack can be indicated by
before age three. The risk for children
the presence of tiny molecules called
without autoantibodies was only 0.4
islet autoantibodies. Now, findings
percent by age 15.
from a new study strengthen the link
“These findings will help us to better
between autoantibodies and the risk
identify children who are at the highest
of developing T1D and highlight the
risk for developing type 1 diabetes and
importance of prediabetes research for
allow scientists to focus prevention
disease prevention.
efforts on groups who are most likely
to become insulin dependent,” says
Jessica Dunne, Ph.D., senior scientist
at JDRF. “Prevention of the disease is a
priority for JDRF, and it is work like this
that sets the stage for our efforts.”
Drug to Preserve Insulin
Production Shows Promise
A potential drug for protecting
the insulin-producing beta cells in the
pancreas that was once considered
stalled is coming back to life, thanks
to JDRF-funded researchers. Three
years after an experimental drug for
T1D called teplizumab failed to pass
all the hurdles in the Phase III trials,
results from a new study prove it
may be effective at preserving beta
cell function—and ultimately insulin
production—in some people with
recent-onset T1D.
Kevan Herold, M.D., professor of
immunobiology and deputy director
for translational science at Yale
University, treated 52 newly diagnosed
8- to 30-year-olds with teplizumab
for two weeks at T1D diagnosis and
again one year after diagnosis. Dr.
Herold and his research team tracked
levels of c-peptide (a marker of the
beta cells’ ability to produce insulin)
in a trial group and a placebo group
younger subjects. Nevertheless, they
islet cells has been successful for an
for two years. Results show the drug
are excited by the efficacy of the drug.
indefinite period of time without the
significantly reduced the loss of
“Some of our patients and families
use of immunosuppressive drugs.
c-peptide two years after the initial
have described a real impact on their
treatment. In fact, c-peptide levels were
diabetes,” Dr. Herold says.
in Diabetes, a research team led by
75 percent higher in those treated with
Key point: JDRF-supported scientists
Stephen D. Miller, Ph.D., the Judy
teplizumab compared to the placebo
group. Drug-treated subjects retained
more detectable insulin production
and required less injectable insulin
to maintain healthy hemoglobin A1c
levels. The findings of the JDRF-funded
study will be published in Diabetes.
Not all trial participants responded
tested the drug teplizumab in
newly diagnosed people with T1D.
Some of the subjects treated with
the drug retained more detectable
insulin production and required less
injectable insulin than the placebo
group, giving researchers new hope
for treating new-onset cases of T1D.
to teplizumab—some lost more than
40 percent of their ability to produce
insulin, similar to many of the control
subjects not receiving the treatment.
Those who benefited the most had
Interspecies Transplant
of Islets a Possible Therapy
for T1D
In a new study recently published
Gugenheim Research Professor
of Microbiology–Immunology at
Northwestern University Feinberg
School of Medicine, was able to
modify the immune systems of mice
to recognize rat islets as their own
and not reject them. The mice were
monitored for 300 days, during which
time 100 percent of the transplanted
islets continued to produce insulin.
The ultimate goal is to be able to
transplant pig islets into humans, as
pig islets make insulin that can control
relatively good control of their blood-
For people with T1D, receiving
blood-glucose levels in humans, the
glucose levels and only a moderate
transplanted islet cells from a
researchers say.
need for insulin injections when
deceased donor can help restore beta
the treatment began. The different
cell function and insulin production.
acknowledge that it is probably easier
responses likely involve variations in
But there is a severe shortage of
to get mice to accept tissue from rats
the metabolic condition of the subjects
donor pancreases, and a large
than to get a human to accept islet
and in the severity of their disease
number of people with T1D can
cells from a pig, they did stress that
at the trial’s start, the researchers
suffer serious kidney, eye, or nerve
this is a first step toward interspecies
reported.
damage while waiting for a donor.
islet transplants without the need for
“The benefits of treatment among
To solve this problem, scientists
the patients who still had moderately
would like to transplant islets from
healthy insulin production suggests
another species to restore insulin
that the sooner we can detect the
production, and provide greater
prediabetes condition and get this
availability, for people with T1D. The
kind of drug on board, the more
process of transplanting an organ, cells,
people we can protect from the
or tissue from one species to another
progressive damage caused by an
is called xenotransplantation. It carries
autoimmune attack,” says Jeffrey
an extremely high risk of the body
Bluestone, Ph.D., the AW and Mary
rejecting the donor tissue—meaning
Clausen Distinguished Professor of
transplant recipients must take life-
Medicine, Pathology, Microbiology,
long immunosuppressive drugs to keep
and Immunology at the University of
the cells alive and decrease the risk
California, San Francisco. Dr. Bluestone
for infections or disease. But JDRF-
co-led the study and was a developer
funded researchers have taken the
of teplizumab.
first step toward effective animal-to-
The researchers note that 94
human islet transplants by successfully
percent of the participants were
transplanting insulin-producing islets
under age 18, and the normal rate
from one species to another—the first
of c-peptide decline is greater in
time that an interspecies transplant of
Although the researchers
immunosuppressive medications.
Key point: JDRF-funded researchers
at Northwestern University have
successfully transplanted insulinproducing islets from one species
to another without the use of
immunosuppressive drugs. One
hundred percent of the transplanted
islets produced insulin for 300 days.
The study opens a new path toward
using an alternative and plentiful
source of islets from another species
to produce insulin in people with T1D.
Nanoparticle-Based Vaccine
Progresses
Identifying the immune-system
attack that causes beta cell death—
and ultimately T1D—can be tricky,
even for the most skilled scientists.
It would be ideal if a medicine or
vaccine could deliver therapies
straight to the malfunctioning part
of the immune system to treat
the disease. Now, JDRF-funded
researchers are trying to do just that
by using nanoparticles (engineered
microscopic particles) to deliver
immune regulation to people with
T1D. New insights into the workings
of the immune system—and how it
interacts with components delivered
by nanoparticles—have given scientists
a unique angle from which to develop
a nanoparticle-based vaccine for T1D.
At a workshop held at the recent
Federation of Clinical Immunology
multiple autoimmune and allergic
of glucagon to treat hypoglycemia via
diseases.”
an insulin pump. Glucagon is a naturally
JDRF has long been a leader in
funding nanoparticle research and
to hypoglycemia by increasing the
is looking to focus its efforts on
amount of glucose in the blood.
developing a nanoparticle-based
It works in concert with insulin to
vaccine. One approach JDRF supports
maintain optimum blood-glucose
is called antigen-specific therapy,
balance.
which targets certain autoimmune
unstable substance that cannot long
immune responses produced by
maintain its molecular integrity after
antigens. Because the nanoparticles
being dissolved in liquid, providing a
can be tailored to induce a response
short window of therapeutic viability—
to a specific autoimmune disease, they
in liquid form it requires refrigeration
should minimize side effects and allow
and therefore cannot be used in current
better control over the precise immune
insulin pumps. A stable formulation
response.
of glucagon could not only improve
The workshop also piqued the
daily treatment regimens for people
industry who attended, including
with T1D, it could also facilitate the
those eyeing these nanoparticle-based
development of bihormonal closed-
vaccine approaches to add to their
loop artificial pancreas systems.
autoimmune-disease portfolios.
Boston, JDRF brought together
resources and efforts in nanoparticle-
leading researchers and industry
based vaccines to advance potential
executives to discuss new ways to use
treatments forward into clinical trials.
nanoparticles to treat and prevent T1D
JDRF-funded investigators and industry
and to present updates on the progress
executives met at a workshop to
made with their respective approaches
discuss new ways to use nanoparticles
to developing a nanoparticle-based
to treat T1D and to update one
vaccine. The JDRF-funded investigators
another on their progress developing
presented everything from optimized
nanoparticle-based vaccines.
nanoparticle design and delivery
ultimately regulatory approval.
“Impressive progress has been made
by these JDRF-supported nanoparticlebased T1D vaccine projects, which
are at the forefront of the field,” says
Richard A. Insel, M.D., chief scientific
officer at JDRF. “These vaccines
encompass platform technologies that
have potential to prevent and regulate
the autoimmune response associated
with T1D and to be applicable to
both the ease and effectiveness of
interest of the many members of
Key point: JDRF is sharpening its
treatments into clinical trials and
However, glucagon is a particularly
reactions without impairing critical
Societies (FOCIS) conference in
methods to ways to advance potential
occurring hormone that responds
JDRF Inks Partnerships for
Soluble Glucagon
About 400,000 Americans
For the artificial pancreas to become
an automated, closed-loop system,
new technologies and drugs, including
stable, pumpable glucagon, will be
required in order to more closely
and accurately mimic the functions
of a healthy pancreas. JDRF recently
announced two partnerships to support
the development of a soluble glucagon
formulation with Xeris Pharmaceuticals
and Latitude Pharmaceuticals. The
companies will each develop a different
approach to making glucagon usable
for infusion pumps.
Xeris—a specialty pharmaceutical
company based in Austin, TX, focused
with T1D use insulin pumps to help
on developing injectable therapeutics—
manage blood-glucose levels and
will study its stable, room-temperature,
treat for episodes of hyperglycemia
and non-aqueous injectable glucagon,
(high blood glucose), but a major
named G-Pump™ Glucagon, to treat
barrier to a wider acceptance of the
hypoglycemia. Clinical studies will
current insulin pumps is their inability
take place at Oregon Health & Science
to correct potentially dangerous
University (OHSU) with two years of
hypoglycemia (low blood glucose).
milestone-based funding from JDRF.
One possible treatment option for
better blood-glucose control is the use
the principal investigator at UVA of
Key point: Boris Kovatchev, Ph.D,
Latitude will use a unique, proprietary,
the JDRF Artificial Pancreas Project.
director of the University of Virginia
solvent-free, glucagon nanoemulsion
This international, multicenter project
Center for Diabetes Technology and
called Nano-G to solubilize and
is designed to test and advance
a leading player in the efforts to
stabilize the molecule, so that it does
artificial pancreas systems, which
advance artificial pancreas technology,
not degrade and remains biologically
could help ease much of the burden
was honored by JDRF with the
active. With milestone-based funding
of managing T1D. He designed and
prestigious Gerold and Kayla Grodsky
from JDRF for one year, Latitude plans
developed the use of in silico modeling
Basic Research Scientist Award. Dr.
to begin clinical testing in the United
and simulation, which has significantly
Kovatchev has spent more than 20
States in 2014.
reduced the time and cost of algorithm
years as a mathematical modeling
Key point: JDRF announced
testing in animal models prior to use in
and computing researcher, focusing
humans—a tool endorsed by the U.S.
mostly on diabetes translational
Food and Drug Administration and
research, and has pioneered advances
now used around the world.
on artificial pancreas systems,
Meanwhile, San Diego-based
two partnerships to support the
development of a soluble glucagon
formulation with Xeris Pharmaceuticals
and Latitude Pharmaceuticals. A
stable formulation of glucagon
could not only improve both the
ease and effectiveness of daily
treatment regimens for people
with T1D, it could also facilitate the
development of bihormonal closedloop artificial pancreas systems.
Researcher Honored for
Leadership and Innovation in
T1D Research
Boris P. Kovatchev, Ph.D., a
Dr. Kovatchev also led a team in
creating a portable cell phone–based
system that has allowed mobile testing
of artificial pancreas systems, and he
has led one of the first sites testing
artificial pancreas systems in real-world
conditions. In addition, Dr. Kovatchev
has authored more than 136 peerreviewed publications, lectures around
the world on diabetes technology, and
holds 36 U.S. and international patents.
“We are thrilled to be honoring Dr.
Kovatchev, whose leadership in the
JDRF Artificial Pancreas Consortium
pioneering researcher at the University
has been paramount in advancing
of Virginia (UVA) and a leading player
the field,” says Richard A. Insel,
in the efforts to advance artificial
M.D., JDRF’s chief scientific officer.
pancreas technology, was honored
“Recognizing the wealth of talent and
with the prestigious Gerold and Kayla
breadth of influence that Dr. Kovatchev
Grodsky Basic Research Scientist
has offered to type 1 diabetes research
Award at JDRF’s OneConference,
is what this award is all about.”
held recently in Washington, D.C. The
annual award recognizes leadership
and innovation in T1D research and was
this year presented by its namesake,
esteemed researcher Gerold Grodsky,
Ph.D.
For more than 20 years, Dr.
Kovatchev has lent his talents to
the field of mathematical modeling
and computing, focusing mostly
on diabetes translational research.
Among his contributions to diabetes
research, Dr. Kovatchev is currently
which could help ease much of
the burden of managing T1D.