The News:

JDRF-funded researchers at the La Jolla Institute for Allergy and Immunology have proven that CD-8–the destructive, renegade player in the immune system that attacks insulin-producing beta cells in mice–is in fact the same T-cell that kills beta cells in humans.

What This Means for the T1D Community:

We know a lot about type 1 diabetes in mice.  Researchers have CURED type 1 diabetes in mice.  There are people (I’m not one of them) who are tired of hearing about mice.

This discovery is so important because researchers have proven that what they know is true in mice, is also true in humans.

Matthias von Herrath, M.D.

And these guys haven’t proven just anything.  What they have observed is at the root of T1D.  If we can actually witness the attack of a certain type of cell by another type of cell, at a certain location in the pancreas, we can effectively begin to halt that attack.

And while this next idea is slightly hard to think about, this crucial breakthrough in CD8 is a result, in large part, of a JDRF-run program called nPOD.

NPOD (Network for Pancreatic Organ Donors with Diabetes) is a program in which human cadaveric pancreatic tissue–which is extremely hard to come by–is distributed to the the researchers who will, essentially, make the best use of it.

These guys–immunologists who study a system that has had millennia to make itself complex enough to effectively outwit disease–have made very good use of nPOD.

JDRF’s ability to coordinate programs like nPOD, its ability to assess researchers, its deftness in coordinating the many efforts to cure this disease . . . all of this convinces me that we really are one step closer.

If You Want to Read More:

JDRF’s Press Release

nPOD Site

The research abstract

Story in Science Daily

Your tax-deductible gift will help JDRF fund an expanded approach to cure, treat, and prevent type 1 diabetes.

Dear Friends:

This time of year, I always give thanks for those who are important in my life. And because of your support of JDRF, I count you among that special group.

I am a long-time JDRF volunteer who grew up with a brother with type 1 diabetes. Sadly, he passed away from complications at an early age. A few months later, I was diagnosed. So, my fight to find better treatments and a cure for type 1 diabetes is very personal. But that is also why I so deeply appreciate the support of others like yourself who may not have as personal a connection. And why I’m asking you to consider a year-end gift to JDRF.

Today, I have an even more powerful reason to support JDRF: a seven-year-old granddaughter. My worst fear is that she will fall victim to this life-threatening disease. JDRF is making significant progress in the area of prevention, to stop the development of type 1 diabetes in those most at risk. Those like my granddaughter.

Prevention is just part of the expanded approach JDRF is taking to both improve the lives of those with T1D today, while curing type 1 diabetes tomorrow. The good news is that the research opportunities and pathways to real solutions are greater than ever. The challenge is that bringing them to those whose lives they will change is more expensive than ever.

That’s why I’m giving more to JDRF. And why I’d like to ask you to consider JDRF in your year-end giving plans. You can rest assured that your donation is well invested, as more than 80% of every dollar JDRF spends goes to help cure, treat, and prevent T1D. And you’ll know that you have helped hasten the day when type 1 diabetes no longer threatens the lives of those we love. Thank you for your generosity, in both spirit and financial support. And thank you for joining us in improving lives and curing type 1 diabetes.

Sincerely,

Last week, JDRF-funded researchers from the La Jolla Institute for Allergy and Immunology in San Diego, California announced that they had created the first 3-dimensional movies depicting the destruction of insulin-producing beta cells – the process that ultimately leads to type 1 diabetes (T1D) – in real-time mouse models. Their research was published in this month’s Journal of Clinical Investigation.

So much of T1D goes unseen by patient and physician alike. A patient often is not even diagnosed until the disease progression has reached a point that can be potentially dangerous. Even the researchers tasked with studying the disease and its cause(s) have done so largely by observing the effects of the disease – the symptoms from the overall reduction in the beta cell population – instead of being able to actually see the beta cells as they are destroyed.

The basis for the new imaging is a two-photon microscope and a new technique developed by JDRF Scholar, Dr. Matthias von Herrath to access the pancreas. The JDRF Scholar program was initiated in 2006 to support pioneering, potentially breakthrough research. Using intense light pulses, the microscope is able to visualize the cells of the pancreas as well as the blood vessels being used by immune T cells to access the pancreas. These blood vessels are important as they are allowing the immune T cells to enter the pancreas where they would not normally exist.

Researchers are already benefiting from these movies, gaining a better understanding of the process and speed with which the beta cells are destroyed by the immune cells. By watching in real time, the researchers observed that the process of beta cell death happened much slower than previously believed, requiring tens of millions of T cells to destroy a significant number of beta cells. This finding provides a potential explanation for the relatively long preclinical stage of the disease.

This breakthrough at the La Jolla Institute for Allergy and Immunology gives T1D researchers an important tool for studying the disease in its earliest stages in hopes of better understanding how the disease unfolds. Thanks to the high level of detail provided by the videos, researchers have noted specific cellular interactions and behaviors from which they hope to develop a way to halt or prevent the disease process.

Credit: Video by La Jolla Institute for Allergy& Immunology. Published by the Journal of Clinical Investigation.

This video shows the T cells (purple dots) attacking thepancreatic islets (green images), which contain the insulin-producing beta cells. (Beta cell destruction leads to type 1 diabetes). The squiggly “tail” on the T cells, which switches from blue to red to yellow, is atracking mechanism inserted by the researchers to record the T cell’s velocityand attack time. The attack continues over several hours before anumber of beta cells are destroyed.

As new cases of type 1 diabetes (T1D) increase worldwide, JDRF has continued to focus on preventing T1D in those at risk. By the time symptoms of T1D appear, however, the destruction of insulin producing beta cells may have already been occurring for some time. In order to effectively prevent the disease, researchers first need to understand when and how T1D begins, even before symptoms appear. They also need a way to determine whether potential interventions to prevent T1D are working properly.

Researchers involved in a study at Yale University, funded by JDRF and the Lilly Foundation, have announced a breakthrough that may, for the first time, help identify the beginnings of T1D and test new treatments to prevent the disease. In new findings published in Proceedings of the National Academy of Science, the research team, led by Dr. Kevan Herold, reports the discovery of a new blood test that may be able to detect the loss of pancreatic beta cells in those at risk of developing T1D prior to disease diagnosis.

In this study conducted in mice, the researchers developed a non-invasive method to detect beta cell loss by looking for the appearance of DNA released by dying beta cells into the blood. Specifically, they looked for the portion of DNA containing the insulin gene, which they distinguished from DNA released by sources other than dying beta cells. When they used this test to analyze the blood of mice as they developed diabetes, the researchers found that they could detect the beta cell insulin DNA as soon as beta cells began to die, even before blood sugar began to rise and the mice developed symptoms of diabetes. Initial data using human blood samples demonstrated that the same type of test may detect beta cell loss in people with recent-onset type 1 diabetes before symptoms begin to appear.

These promising results suggest that one day this test could be used to monitor beta cell loss in individuals at risk for and in the early stages of type 1 diabetes, although more work will be required to develop a test that can be used in a physician’s office. In addition to diagnosing and monitoring T1D, this method could help test new drugs aimed at protecting beta cells and preventing T1D’s onset.

Methods to detect beta cell loss, such as the one discovered by Dr. Herald’s team, are critical, according to Dr. Andrew Rakeman, Senior Scientific Program Manager at JDRF. “Dr. Herold’s work has the potential to develop a tool that will not only allow us to better understand the fate of beta cells in type 1 diabetes,” explains Dr. Rakeman. “It will also help guide the development of clinical trials aimed at protecting or preserving beta cells in T1D by allowing us to select the most appropriate patient population and providing a marker for whether the therapy is working.”

At the recent American Diabetes Association 71st Scientific Sessions in San Diego the results of several clinical trials focused on finding a cure for type 1 diabetes were announced.

Most of these trials tested drugs administered to people with type 1 diabetes to curb the autoimmune attack on the beta cells. If scientists can determine a way to control the autoimmune response involved in type 1, along with methods of either regenerating or replacing the lost beta cells, the combination of these areas of research could result in a cure for type 1.

Two of the clinical trials showed efficacy and met their primary endpoints (that is, they satisfied pre-determined parameters of success) and another, while not a success by clinical standards, did reveal some clues as to how scientists can continue to refine these drug therapies to be more effective and impactful for people with type 1.

The first trial, known as the AbATE trial, tested an anti-CD3 drug therapy (known as teplizumab). The Phase II trial was successful in slowing the progression of type 1 diabetes in people with newly diagnosed disease. Individuals in the teplizumab arm received two separate 14-day courses of the drug, once at the beginning of the study and once 12 months later. Trial participants had higher levels of C-peptide (indicating the presence of naturally produced insulin in the body) at 24 months after treatment and lower insulin needs at 12 and 18 months after treatment compared to a control group that received a placebo drug.

A second trial, also Phase II (testing a drug called CTLA4-Ig or Abatacept) also showed treated participants as having higher levels of C-peptide than participants who had received a placebo at two years after treatment, as well as lower A1C levels, indicating better control of blood sugar levels.

A third trial, known as the Protégé trial, showed mixed results. While the Phase III Protégé trial, also conducted with the anti-CD3 drug teplizumab, did not meet its pre-determined endpoints when the data is viewed as a whole, certain sub-groups of participants responded well to the drug therapy. Children between the ages of 8 and 11 years old, participants who had been diagnosed within six weeks of receiving the first dosage, participants who received longer, higher-dose regimens of the drug, and participants in the United States had evidence of preserved beta cell function at 12 months after treatment was begun.

JDRF will provide a more detailed report on all results coming out of the Scientific Sessions in an upcoming issue of Countdown, JDRF’s online magazine.

If you’d like to find out more about clinical trials or participate in one, please visit the JDRF Type 1 Diabetes Clinical Trials Connection.

In addition to JDRF’s commitment to finding a cure and providing better treatments for all type 1 diabetics, we are also interested in preventing the onset and progression of the disease. A three-year $500,000 grant from JDRF will help researchers look more closely at a specific protein deficiency that could signal the onset of type 1 diabetes.

Read the article at EndocrineWeb.com

Expanded program intends to accelerate promising ideas from academia into drug development pipeline

JDRF announced today it has extended its jointly-funded research program with the Johnson & Johnson Corporate Office of Science & Technology (COSAT), which focuses on increasing the development of possible therapeutics that will promote pancreatic beta cell survival and function in individuals with insulin-dependent diabetes.

Preserving beta cell function in individuals at all stages of type 1 diabetes (including at-risk) and even those with insulin-dependent type 2 diabetes could mean a number of things, all of which have the potential to result in a tremendous improvement in the quality of life for those living with the disease:

• Individuals might develop the disease at a slower rate, or perhaps never even develop the onset of type 1 diabetes
• Individuals with type 1 diabetes might require less or even no insulin
• Individuals with type 1 diabetes could potentially have more stable blood sugar levels and reduced risk of hypoglycemia
• All of the above could mean less risk of short-and long-term complications for those living with the disease

“Developing therapies that will preserve beta cell function could solve one of the fundamental challenges facing researchers. If we can devise treatments to protect functional beta cell mass, it may be possible to slow the progression of type 1 diabetes or prevent it entirely in individuals at risk for the disease,” said Patricia Kilian, Ph.D., Director of Beta Cell Regeneration for JDRF.

The joint program funds research to identify specific molecules involved in beta cell survival and death. “If we can then discover and develop drugs that pinpoint these vulnerable areas, we could have a new approach to preserving beta cell function in type 1 diabetes,” added Kilian.

Initially announced in December 2009, the program has funded three promising beta cell research projects at leading academic laboratories – and the expanded program intends to double the number of jointly funded projects, thereby accelerating the translation of basic research into potential beta cell therapies for diabetes.

“This partnership is a prime example of how JDRF is working with companies to translate promising academic research into clinical realities for people with type 1 diabetes,” said Karin Hehenberger, M.D., Ph.D., Senior Vice President of Strategic Alliances for JDRF. “It harnesses the strengths of both JDRF and COSAT to identify and support research ideas that may produce novel insights about the disease and new targets to advance the drug discovery and development process.”

h3>Bridging the Gap

JDRF’s partnership with COSAT is an integral part of a larger organizational initiative that addresses promising areas of research together with industry. Many promising early-stage diabetes technologies discovered within academia often don’t move on to become therapies due to a lack of funding. By supporting these novel technologies, we can ensure they make their way through to industry where they can be tested fully and ultimately developed into products for patients.

JDRF and COSAT, working with Johnson & Johnson Pharmaceutical Research & Development, LLC (J&JPRD), are soliciting grant proposals from academia and medical research institutions for one- or two-year projects. Funding recommendations will be led by a combined review committee consisting of representatives from JDRF, COSAT, and J&JPRD, with oversight from a Scientific Advisory Board and JDRF volunteers.

Researchers are working to determine how genetics and environmental factors contribute to the development of type 1 diabetes.   A number of recent studies have indicated that enteroviruses – common viruses that can cause cold-like symptoms, fever, or diarrhea – may be linked to the development of type 1 diabetes. A new study published in the journal BMJ provides further evidence that these viruses play a role.

The new study was a meta-analysis, meaning the researchers did not conduct any new human trials, but reviewed and compared existing data from nearly 5,000 people with type 1 diabetes to draw their conclusions. Based on the data, the researchers concluded that there is a clinically significant association between enterovirus infection and type 1 diabetes.

It’s important to note that the study only shows an association between enteroviruses and type 1 diabetes. It does not establish a cause and effect relationship, nor the process by which the autoimmune attack that causes type 1 is triggered.

The idea that viruses may be associated with the development of type 1 diabetes is certainly not new. So why, then, is a study like this one important? According to the researchers involved, understanding the role viruses play in people who develop type 1 diabetes produces knowledge that could possibly be applied to strategies to prevent the disease. Understanding the causes of type 1 diabetes could, for example, lead to a vaccine to prevent it from occurring in the first place.

JDRF shares the point of view that the knowledge we gain about the underlying causes and development of type 1 diabetes from research will be vital for developing preventive approaches.   JDRF’s Chief Scientific Officer, Dr. Richard Insel, provided a comprehensive overview of prevention research in a recent webcast, which can be seen in the video box on the right-hand side of this page.

Tune in Tuesday, Jan. 25, 2011 at 11:00 a.m. (Pacific Time) online at: www.jdrf.org/livewebcasts

Happy 2011!

We’re kicking off our first webcast of the new year with a live Q+A session with JDRF’s Chief Scientific Officer, Dr. Richard Insel.

This month, we’re going to focus on research in the prevention of type 1 diabetes. At its core, the goal of prevention science is to prevent type 1 diabetes from developing in people who are at risk for the disease. But prevention research may also have important benefits for people currently living with type 1 diabetes.

Some of the topics Dr. Insel will address include:

• What research is JDRF doing to understand the causes of type 1 diabetes? Is it in the genes? Is it caused by the environment?
• What is being done to prevent the disease from developing in those at risk?
• How will prevention research help people who already have type 1 diabetes?
• Are there any promising treatments out there now that can prevent or delay the onset of type 1 diabetes?
• What kinds of clinical trials are available today that families affected by type 1 diabetes can join to reduce the likelihood of more family members developing type 1 diabetes?

The incidence of type 1 diabetes has steadily increased over the past couple of decades. An estimated 3 million Americans currently have type 1 diabetes, and approximately 15,000 adults and 15,000 children are diagnosed with the disease every year.

Submit your questions via live chat at www.jdrf.org/livewebcasts this coming Tuesday, Jan. 25, at 11:00 PM PST. The program is scheduled to last 1 hour.

You may also ask your questions via email by sending them to webcast@jdrf.org.

Preliminary findings reported by researchers at the University of Helsinki in Finland suggest that a certain type of infant formula could play a role in preventing type 1 diabetes in children who are at risk for developing the autoimmune disease. Initial results from the study, published recently in the New England Journal of Medicine, found some evidence that infants at risk for developing type 1 diabetes who were fed a specialized formula after breastfeeding were less likely to develop autoantibodies associated with type 1 diabetes, when compared with those who received formula made with cow’s milk.

The study is the pilot in Finland for a larger, on-going international trial called TRIGR (Trial to reduce Insulin-dependent diabetes in the Genetically at-Risk), which is designed to determine whether weaning to a specialized formula decreases the risk of developing type 1 diabetes. The larger study involves more than 2,160 infants in 15 countries (including those featured in the Finland study) and tracks the children up until their 10th birthday for the presence of diabetes-related antibodies and the development of diabetes. All of the participants in the study have a genetic susceptibility to diabetes, and had at least one family member with type 1 diabetes.

In the study, the research group led by Dr. Michael Knip of University of Helsinki gave formula that was “hydrolyzed,” or broken down into smaller proteins that makes it easier to digest, to half of the 230 infants participating in the study, while the other half were fed with the cow’s milk formula. Infants in the study were monitored for 10 years. Those who received the specialized formula showed that it reduced the presence of diabetes-related autoantibodies, suggesting that the hydrolyzed formula may ultimately be shown to have a role in the prevention of type 1 diabetes.

“The preliminary results from this study could shed additional light on a possible way to prevent the onset of type 1 diabetes in individuals who have been identified at risk for the disease,” Dr. Insel added. “I look forward to seeing the results of the larger TRIGR study, which will provide further insight and evidence into the role that cow’s milk formula is a risk factor for developing type 1 diabetes,” he added. Final results of the study are expected to be completed in 2017.

TRIGR is the largest type 1 diabetes prevention trial to date, and is one of many important developments in diabetes research that is currently being supported by the Special Diabetes Program (SDP), a federal-funded program that is up for renewal before Congress. Without continued funding for the SDP, support for much-needed clinical research, like TRIGR, will be in jeopardy.

Established by Congress in 1997, SDP currently funds $150 million annually for type 1 diabetes research, representing 35 percent of the federal government’s support for type 1 diabetes research. JDRF, also committed to funding research toward a cure for type 1 diabetes, is calling for the multi-year renewal of the program before Congress adjourns for the year. “If the SDP is renewed, this would ensure that the discoveries and advancements made based on this study can continue uninterrupted to further our mission of treating and curing type 1 diabetes,” added Dr. Insel.

Key highlights:

• While not definitive, early evidence provides clues on a possible link between the diet of at-risk infants and prevention of type 1 diabetes.
• The study is the pilot for a larger, on-going trial called TRIGR, which is designed to determine whether weaning to a highly hydrolyzed formula decreases the risk of developing type 1 diabetes.
• Renewal of the Special Diabetes Program will help ensure that the research for TRIGR study continues until its completion in 2017.

About JDRF

JDRF is a leader in setting the agenda for diabetes research worldwide, and is the largest charitable funder and advocate of type 1 research. The mission of JDRF is to find a cure for diabetes and its complications through the support of research. Type 1 diabetes is a disease which strikes children and adults suddenly and requires multiple injections of insulin daily or a continuous infusion of insulin through a pump. Insulin, however, is not a cure for diabetes, nor does it prevent its eventual and devastating complications which may include kidney failure, blindness, heart disease, stroke, and amputation.

Since its founding in 1970 by parents of children with type 1 diabetes, JDRF has awarded more than $1.4 billion to diabetes research, including more than $100 million last year.