Research Update

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2010 marks the 40th anniversary of JDRF’s founding.

In 1970, a handful of parents of kids with type 1 diabetes got together and made a promise to one another, and to their children. They were going to do all they could to find a cure for type 1 diabetes, combining and concentrating their resources. And research would be the tool they used.

As a reminder of how far we have come – and to renew the hope we all have for a cure – we wanted to highlight some of the research advances made over the decades.

In the 1970s…
Hormones that can improve the effect of insulin are discovered, purified, and synthesized, including glucagon, an important treatment for low blood sugars (hypoglycemia)…JDRF scientists define the "tumor angiogenesis factor," the abnormal growth of blood vessels in the eye caused by diabetes…The first test to measure long-term blood sugar levels – the hemoglobin A1c test – is developed, with significant JDRF scientific backing.

In the 1980s…
JDRF-funded science leads to the development of genetically engineered insulin…JDRF scientists help to better understand and prevent the chronic effects of low blood sugar on the brain…JDRF scientists show that blood sugar control is the key to fetal development, leading to treatment standards that revolutionize pregnancies for women with type 1 diabetes – and the delivery of healthy babies.

In the 1990s…
To help prevent diabetic arteriosclerosis, scientists discover a drug that keeps glucose from blocking blood vessels…JDRF research establishes that high blood sugar levels lead to increased risk of diabetic eye disease…JDRF establishes the Human Islet Distribution Programs to meet the growing need for insulin-producing cells for transplants and research towards a cure following other paths

In the 2000s
JDRF establishes the Immune Tolerance Network with the NIH to prevent the immune response that causes type 1 diabetes…JDRF researchers develop the Edmonton Protocol for islet transplants, which greatly improves the success rate for transplanting insulin-producing cells in people with brittle diabetes…JDRF clinical trials show that treating newly diagnosed patients with a drug called an anti-CD3 antibody can save insulin-producing cells for several years – a major step towards stopping diabetes in its early stages, and reversing it in people with established diabetes…Clinical trials use new treatments to reduce the risk of severe hypoglycemia in children…Genetic studies show that a specific gene variant protects people from diabetic kidney disease…Researchers discover that insulin-producing cells can successfully replicate, offering great promise in the field of regeneration as a potential diabetes cure…JDRF clinical trials definitively show that people with type 1 diabetes who regularly use continuous glucose monitors (CGMs) to help manage their blood sugar experience significant improvements in blood sugar control without increasing their risk of low blood sugar emergencies – leading to increased insurance coverage of CGM devices…JDRF collaborates with industry, academia, insurers, and regulatory agencies to drive the development of an artificial pancreas – a system that will link a CGM with an insulin pump via a sophisticated computer program.
The research advances of the past 40 years – and the quickening pace of science of the past decade – is inspiring. But we are not celebrating our 40 years – because we have not yet kept the promise those founding families made to one another, and to their children. We still don’t have a cure.

Rest assured, we will find it. After all, this is a promise that goes back 40 years, back to the first days of JDRF. A promise that is just as important today as it ever was.

JDRF has four cure therapeutic areas. These four targeted areas of research , and the priority areas within each provide us the focus to find a cure FASTER. This research strategy, along with the partnerships needed to move forward will accelerate our path to a cure. Our four areas of research are: Beta Cell Therapies, Immune Therapies, Glucose Control and Complications Therapies. Take a look at some of the progress made in each.

JDRF Key Advances
Spring 2010
Thanks to the generous support you and other donors have given, JDRF’s research program has made significant advances in recent months toward our goal: to find a cure for type 1 diabetes and its complications. We rely on people like you to help move science along as rapidly as possible. Below are highlights of the recent accomplishments you helped make possible.

Immune Therapies
Phase II Study Reveals Long-Term Benefits Of Anti-CD3 Antibody Treatment
A JDRF-supported clinical trial in Brussels, Belgium, has found that a six-day treatment with anti-CD3 antibodies can slow the normal rise in insulin use in the first few years after a diagnosis of type 1 diabetes. This shows that the treatment, although brief in duration, was able to preserve the function of insulin-producing cells for several years – a major step toward stopping or slowing the disease’s progression. The trial also points to the importance of early intervention, as those who benefited from the treatment were younger at the time of diagnosis and had greater initial beta cell function.

What this may mean for people with type 1 diabetes: Anti-CD3 antibodies remain an important potential treatment for the newly diagnosed. Clinical trials of immune therapies like anti-CD3 also add to the body of knowledge about type 1 diabetes – helping scientists better understand the disease and develop the best possible therapies for people at all of the stages of type 1 diabetes: the at-risk, the newly diagnosed, and those who have had type 1 for years.

An Oral Vaccine Using “Yeast Shells”
JDRF-funded researchers are developing an oral vaccine to control the autoimmune response that causes type 1 diabetes. The unique approach uses hollow “yeast shells” derived from baker’s yeast to carry proteins and other agents that alter the behavior of immune cells in the stomach. If effective, the vaccine will retrain the immune system to tolerate the insulin-producing beta cells that are mistakenly targeted and destroyed in type 1 diabetes.

What this may mean for people with type 1 diabetes: This research is an important example of the innovative, clinically directed research taking place within JDRF’s Immune Therapies program. The novel strategy has the potential to address the root causes of type 1 diabetes and thus holds the promise of benefiting all people with type 1.

Beta Cell Therapies
JDRF-Funded Researchers Identify Gene Critical to Development of Insulin-Producing Cells
Researchers have identified a gene that is required for the development of insulin-producing cells and other cell types in the pancreas. They found that mice lacking the gene (called Rfx6) failed to generate insulin-producing beta cells and most other normal cell types in the pancreatic islets. They also found that, in people, deficiency of the Rfx6 gene resulted in diabetes in newborns.

What this may mean for people with type 1 diabetes: This work reveals the importance of Rfx6 in the body’s natural production of insulin-producing cells – and thus identifies a new target from which to develop potential treatments for type 1 diabetes. Further research on the gene may help scientists discover how to produce replacement beta cells or to develop therapies to regenerate beta cells.

Stress Hormone Is Linked to Beta Cell Growth, Providing Potential New Therapeutic Target
A hormone responsible for the body's stress response has been linked to the function and growth of the insulin-producing beta cells. When beta cells were exposed to the hormone (called CRF) and to high levels of sugar, they produced and released insulin and began to grow faster. The study was led by JDRF-funded researchers at the Salk Institute for Biological Studies in California.

What this may mean for people with type 1 diabetes: The findings reinforce the potential of regeneration as a cure for diabetes and also provide insights for discovering new approaches to treat the disease.

Two New Partnerships in Regeneration Help Drive Towards a Cure Faster
JDRF has entered into two key collaborative agreements that will quicken the pace of progress toward cures and treatments for type 1 diabetes. The first – one of the largest and most comprehensive collaborations in JDRF’s 40-year history – is with the Genomics Institute of the Novartis Research Foundation (GNF). It aims to create a pipeline of potential new regeneration drugs to test in clinical trials. The second is with the Johnson & Johnson Corporate Office of Science and Technology and its affiliates, and it aims to speed the development of drug targets and pathways that promote beta cell survival.

What this may mean for people with type 1 diabetes: The new partnerships will generate a string of potential new beta cell therapies – and further accelerate progress toward a cure.

Glucose Control
En Route to Developing an Artificial Pancreas
JDRF’s Artificial Pancreas Project (APP) continues to make momentous progress toward the development of an artificial pancreas, a device that can reduce the risk of complications and help to ease the daily burdens of type 1 diabetes. In January, JDRF announced an innovative, non-exclusive partnership with Animas Corporation to develop an automated insulin delivery system – a first-generation artificial pancreas – that will help people with type 1 diabetes better control their disease; Animas is a Johnson & Johnson company and a leading pump manufacturer. A week later, JDRF announced a second partnership, this time with BD (Becton, Dickinson and Company), a leading global medical technology company, aimed at developing novel insulin delivery products to enhance insulin pumps. Most recently, in a landmark study in children and teenagers with type 1 diabetes, JDRF-funded researchers showed that using a first-generation artificial pancreas system overnight can lower the risk of low blood sugar emergencies while sleeping by improving diabetes control.

What this means for people with type 1 diabetes: These developments represent a giant step on the path to achieving an artificial pancreas, a fully automated system that can dispense insulin to patients based on real-time changes in blood sugar levels. Even the earliest systems could bring dramatic changes in the quality of life for the three million people in the U.S. with type 1 diabetes.

Regular CGM Use Increases Control in All Age Groups, Enables Good Control Long-Term
Two more JDRF-funded continuous glucose monitor (CGM) studies have shown that CGM use is beneficial. One study found that regular CGM use – six days per week or more – is the key factor in achieving better diabetes control, more important than the age of the user or other demographic, clinical, or psychosocial factors. The second study found that people who continued using a CGM achieved good glucose control while experiencing a lower incidence of hypoglycemia – the dangerous low blood sugar episodes that can occur with tightly managed type 1 diabetes.

What this means for people with type 1 diabetes: The results underscore the importance of continued research into a closed-loop artificial pancreas, a system that uses CGM technology as one of its key components. There are now four separate publications documenting the benefits of CGM devices.

Complications Therapies
Important New Clues About the Genetics of Diabetic Kidney Disease
JDRF-funded scientists have identified a gene that puts people with type 1 diabetes at greater risk for diabetic nephropathy, a severe and devastating form of diabetic kidney disease that develops in up to 40% of patients with either type 1 or type 2 diabetes. Called ELM01, the gene produces important cell function proteins in key kidney cells and had previously been linked only to type 2 diabetes. The research was an analysis of genetic data collected in the ongoing JDRF GoKinD study (Genetics of Kidneys in Diabetes).

What this may mean for people with type 1 diabetes: This new genetic information, as well as additional clues found through similar research, may eventually enable physicians to identify type 1 patients with low, medium, and high risk for kidney disease. Armed with this knowledge, they could pinpoint the best candidates for therapies and clinical trials aimed at prevention. People who learned they were at higher risk could also take steps to become more vigilant for early signs of the disease. Genes identified in these types of searches also have the potential to be a target for new treatments for diabetic kidney disease.

Blood Pressure Drugs Stop Diabetic Eye Disease from Progressing
Two drugs used to treat high blood pressure can significantly slow the progression of diabetic retinopathy, a serious and common complication of diabetes that can lead to vision loss. According to data from a multi-center clinical trial, type 1 patients with normal blood pressure, no evidence of kidney disease, and very mild eye disease who received either drug – losartan or enalapril – were at least two times less likely to develop more serious complications of diabetic retinopathy than participants not receiving them. The study was built on research co-funded by JDRF in 2002.

What this may mean for people with type 1 diabetes: Complications like retinopathy only add to the burdens of living with type 1 diabetes. This study provides encouraging evidence that the two blood pressure drugs may stem retinopathy in certain people with type 1 diabetes. While further studies will be needed before these drugs can be recommended for routine use, the progress here offers hope for improving the lives of people with type 1 diabetes.

 

For more information on the latest in research, please visit www.jdrf.org!