At the Diabetes Research Institute Foundation, the goal is to cure diabetes, a chronic, life-threatening disease that affects more than 29 million people in the United States, and hundreds of millions more worldwide - at a rate that is rising to epidemic proportions. The discovery of a cure would mean restoring natural insulin production and normalizing blood glucose levels without imposing risks to patients living with this disease. Diabetes Research Institute (DRI) scientists have already shown that transplanting insulin-producing islet cells can restore natural insulin production, eliminate the need for shots, restore normal blood sugar levels and free patients from frightening hypoglycemic episodes. Some patients in clinical trials have been insulin-free for more than a decade. Islet transplantation is the only procedure outside of a full organ (pancreas) transplant that has been able to free patients from insulin injections. Currently, islet transplantation is an experimental procedure, limited to only the most severe cases of type 1 diabetes. One of the main reasons is that patients must take powerful drugs to prevent rejection of the donor cells. Another reason is that are simply not enough donor cells available to treat everyone who can benefit. DRI researchers are working diligently to build upon this progress and address these remaining challenges. The Diabetes Research Institute (DRI) was created for one reason – to cure diabetes – which is and will continue to be its singular focus until our goal is realized.

The DRI is building on its decades of expertise and progress in islet transplantation and immunology research to overcome the remaining challenges to discovering a biological cure for diabetes. Drawing on recent developments in bioengineering, immunology, transplantation and immunogenetics research, Institute scientists are developing the DRI BioHub, a bioengineered “mini-organ" that mimics the native pancreas, containing insulin producing cells that sense blood sugar levels and release the precise amount of insulin needed in real time, together with other components that keep the cells healthy and able to survive long term. An innovative clinical (patient) trial has already begun to test a BioHub platform, and other promising research is now advancing to the clinical phase of testing. The DRI BioHub brings the promise of restoring natural insulin production to millions of children and adults with diabetes by addressing three major challenges: 1. The Site – creating an optimal environment in the body where transplanted islet cells can thrive. 2. Supply – developing an unlimited supply of insulin-producing cells for everyone who can benefit - or enabling patients to regenerate their own cells. Currently, islets come from donor organs, which fall far short of the need. 3. Sustainability – the most critical area for achieving a biological cure, the DRI's priority focus is on overcoming the significant immune system issues by prevent the immune system from targeting and attacking the insulin-producing cells and reversing the autoimmune process that caused the onset of the disease. Multi-disciplinary teams of scientists are simultaneously working on advances each of these areas. Several clinical trials in the Sustainability area have already received approval from the Food and Drug Administration and are poised to begin pending adequate funding.

The DRI is a world leader in cure focused research and is the largest and most comprehensive research center dedicated to curing diabetes. A designated Center of Excellence at the University of Miami Miller School of Medicine, the DRI has made significant contributions to the field of diabetes, pioneering many of the techniques used in diabetes centers worldwide. Few research centers have the ability to translate promising ideas from the lab to the patient. The DRI leverages this ability by housing all phases of research under one roof – translating discoveries from basic research (in the lab), to pre-clinical research (in large animal models), and finally to clinical research (in patients). A unique aspect of the DRI is its core philosophy of collaboration. The Diabetes Research Institute serves as the hub of the DRI Federation, a worldwide alliance of researchers that share knowledge, overcome barriers and accelerate progress. Working closely with these scientific colleagues, researchers at the DRI in Miami investigate more strategies, share more ideas, and accomplish more, bringing promising findings to patients more quickly than ever before. These collaborations also allow philanthropic dollars to go further. Research can be conducted at partner centers in countries with a lower cost basis. We believe that the fastest and most efficient way to end diabetes is to work together toward a cure. The DRI has developed a strategic roadmap for reaching a biological cure for diabetes. First, we've assembled a team of researchers with expertise in the scientific disciplines necessary for attacking diabetes, like bio- and tissue engineers, immunologists, stem cell researchers, molecular biologists, surgeons, clinicians and more. Second, only the most promising research discoveries that can benefit patients advance to further stages of testing so no time or money is wasted. The DRI has become the world leader it is today with the substantial funding provided by the Diabetes Research Institute Foundation. The organization, which began in 1971 with a group of parents who were dedicated to finding a cure for their children who had diabetes, has grown into a coalition of business leaders, celebrities, scientists, clinicians and families is focused on providing the necessary funding to cure diabetes now. The seed funding provided by the DRI Foundation enables DRI scientists to jump-start new research projects and pursue innovative findings. This support fills the gap until grant money is awarded from external funding sources allowing progress to continue without delay - because tomorrow is not soon enough to find a cure.

Assessing progress in the field of scientific research is clearly measurable. Research is conducted using what's commonly known as the “scientific method" which defines the principles and procedures for the systematic pursuit of knowledge involving the recognition and formulation of a problem, the collection of data through observation and experimentation, and the development and testing of hypotheses. In order for an outcome to be accepted, it must prove to be fully replicable. External peer review and evaluation is also important component of the process. Internal and external evaluations are conducted on a regular basis. The DRI's Deputy Directors meet with the scientists and review each project on a monthly basis. The Dean and administration of the University of Miami Miller School of Medicine conduct an independent review as well. The DRI has an external Scientific Review Board comprised of six internationally recognized and highly respected scientists from around the world who review the entire program and present their report to the Dean. The DRI has a policy of discontinuing research projects that are not advancing towards their intended goal of clinical application. Bringing our “mini-organ", the DRI BioHub, to clinical application is the DRI's overarching program. A clinical trial to test a BioHub site and platform is now underway. Other research strategies designed to overcome the challenges of the immune system have received FDA approval to proceed. We anticipate achieving key milestones along the way including: • Optimizing the site which will closely mimic the native pancreas by providing physical support, incorporating vital nutrients and protective agents. • Protecting the transplanted cells from the immune system. Because there are several strategies being tested to achieve this objective, there may be a number of modifications along the way. • The development of an infinite supply of insulin producing cells - and/or enabling patients to regenerate their own cells. The DRI's cell supply team has made exciting progress in this area with one single agent that is already FDA approved for clinical use.

The DRI's goal is to restore natural insulin function in people living with diabetes. The DRI and its collaborators have shown that transplanting insulin producing islet cells makes this possible. Patients participating in clinical islet transplant trials have lived insulin free for more than ten years. The DRI is building upon this progress with a major initiative, the DRI BioHub, mentioned above. The main challenges that must be overcome are: 1) Site: Developing an optimal environment to house and protect the islet cells which mimics the native pancreas; 2) Sustainability: Retraining the immune system to prevent the rejection of transplanted cells without the need for systemic anti-rejection drugs, and reversing the autoimmune attack which is responsible for the onset of type 1 diabetes; 3) Supply: Identifying, developing and/or regenerating an unlimited supply of cells to sense blood glucose levels and produce insulin. Many projects are underway to address these three overarching issues. An FDA-approved clinical trial is now underway to test a new transplant Site in the body. Since medical research involves developing an understanding of previously uncharted territory, DRI scientists are continually expanding and reshaping their work as promising new theories emerge and data is gathered. Successful research outcomes are published in leading peer reviewed scientific journals that substantiate our progress and share it with the scientific community. Beyond the scientific challenges, we face other obstacles. Advancing research from the lab to patients is quite costly. The DRI Foundation (DRIF) provides the DRI with critical seed funding to gather data that is often a prerequisite for larger grants. Economic swings make a huge impact on our ability to raise philanthropic dollars. With federal government cutbacks in place, there have been major reductions in the monies allocated to advance diabetes research by the National Institutes of Health. This places a greater burden on the DRIF to raise the significant funds required to advancing research. We also face the regulatory barriers and complexities imposed by the U. S. Food and Drug Administration (FDA) which significantly increase costs and slow progress. One of the strategies we are employing to avoid these impediments is to work closely with our collaborators in other countries to advance the research outside the purview of the FDA. We are also able to increase cost efficiencies by conducting some of the research including clinical trials outside the U. S.