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Fourth Diabetes Antibody Discovered
JDRF-funded scientists identified a fourth autoantibody in human blood that suggests the earliest stages of type 1 diabetes. The discovery may have great value as a diagnostic tool to more accurately predict who is predisposed to developing diabetes; it also points toward clues indicating how to slow or block the progression of the disease.
Before this finding, three autoantibodies - proteins produced by the immune system that indicate the body is attacking itself - were known for type 1 diabetes. When measured in combination with those three, the presence of the new autoantibody, ZnT8, increased the accuracy of predicting diabetes to 96 percent at disease onset.
The newly identified autoantigen "will find immediate use in identifying individuals with a family history of diabetes or a genetic predisposition to the disease for recruitment into clinical trials aimed at preventing diabetes," said the study's senior author, John Hutton, Ph.D., of the Barbara Davis Center for Childhood Diabetes in Denver.
Four New Type 1 Genetic Regions Identified
An international research consortium identified four new genetic regions that affect risk for type 1 diabetes. This finding, made through a powerful new tool called genome wide association, should help scientists better understand the disease pathway leading to diabetes - which has the potential to lead to new treatments. The finding could also someday provide the means to gain a clearer picture of an individual's risk for developing type 1 diabetes.
The genome wide association method was used by the Wellcome Trust Case Control Consortium, a collaboration of 24 geneticists in the United Kingdom, to examine the genetic basis of many common diseases. As part of this large study, the group identified six chromosomal regions that they suspected of increasing the risk of type 1 diabetes. Researchers at the JDRF/Wellcome Trust Diabetes and Inflammation Laboratory in Cambridge, England, followed up on these findings by examining those same areas using a separate large set of DNA samples. They confirmed that four chromosomal areas are associated with a risk for developing type 1 diabetes.
nPod Helps Advance Study of Diabetes
JDRF launched nPod - which stands for Network for Pancreatic Organ Donors with Diabetes - last August as a means to advance the study of how type 1 diabetes develops and to speed progress toward a cure. The program collects pancreatic tissue and other related tissues, such as lymph nodes, from organ donors with longstanding type 1 diabetes, as well as from those who are islet-autoantibody positive, which indicates that a person is in the early stages of diabetes.
The program marks the first time organ collection has been achieved in an organized, streamlined fashion, and it promises to greatly enhance knowledge about disease development. Already, findings from nPOD have enabled researchers to assess the potential for islet cell regeneration. Contrary to what was previously believed, scientists have learned that some pancreata from people with longstanding type 1 diabetes have insulin-positive beta cells and some have many intact islets. This finding gives hope for the viability of islet cell regeneration or restoration as a treatment for the disease.
JDRF's Industry Program Achieves Goal with Anti-CD3 Therapies
Two of JDRF's Industry Discovery and Development partners entered into global alliances with pharmaceutical companies to develop and commercialize drugs known as anti-CD3 monoclonal antibodies - which interfere in the autoimmune attack - to treat early-stage type 1 diabetes. The agreements demonstrate the success of JDRF's strategy to fill gaps in the drug pipeline by helping small companies move discovery research through early clinical testing until bigger companies step in to fund the large trials needed for FDA approval of drugs and treatments for diabetes.
Lilly and Glaxo SmithKline agreed to develop and commercialize anti-CD3 compounds tested in human clinical trials by MacroGenics and Tolerx respectively, two JDRF industry partners. The JDRF-funded studies at those companies had shown that the anti-CD3 compounds were effective in stopping the progression of the disease in people who had been recently diagnosed with type 1 diabetes.
By funding early-stage testing and validation of anti-CD3 antibodies, including teplizumab at MacroGenics and otelixizumab at Tolerx, JDRF essentially contributed to "de-risking" this therapeutic strategy, making it possible for the biotech companies to advance their antibodies through clinical development, attract additional investors, and secure global licensing and marketing alliances with larger pharmaceutical companies.
Importance of Antigen-Specific Therapy Underscored
A finding from the field of islet transplantation further underscored the importance of developing highly targeted therapies to halt the autoimmune response. Scientists found that in people who received an islet transplant, those who had autoantibodies (which indicate the presence of the autoimmune response) before the procedure were more likely to reject the transplant. Despite the use of immunosuppressive drugs, which lack specificity in tamping down the immune response, these transplant recipients experienced a powerful return of the autoimmune response that causes type 1 diabetes. To address this problem, JDRF is now working to develop antigen-specific therapies that could stop the autoimmune response.
