December 2, 2013
The International Diabetes Federation (IDF) annual meeting (December 2-6, 2013) and Immunology of Diabetes Society (IDS) annual meeting (December 7-11, 2013) in Australia will feature multiple talks on recent findings from the Immune Tolerance Network's ( ITN’s) portfolio of type 1 diabetes studies. Type 1 diabetes is a challenging disease where so far no therapeutic has been able to reverse or permanently halt the autoimmune attack on pancreatic β-cells. Clinical trials with immune modulating agents have had only modest clinical effects, but mechanistic data from these studies is contributing to the growing body of evidence about how cellular changes may relate to clinical outcomes, providing insights into how future treatments should be tailored.
On December 3rd at IDF, Mark Rigby, MD, PhD (University of Indiana) will report on the 18 month results from the ITN’s T1DAL study [Inducing Remission in New Onset T1DM with Alefacept (Amevive®)], which investigated whether alefacept, an engineered fusion protein that targets the CD2 surface molecule on T cells, would preserve pancreatic β-cell function in newly diagnosed patients. At 12 months the treatment group exhibited improvements over the placebo group in important secondary endpoints including 4-hour C-peptide response, insulin use and hypoglycemic events. These positive clinical results were buttressed by an analysis of T cell subtypes of treated patients that showed that effector T cells (inflammatory) were primarily targeted while sparing protective regulatory T cells. These results were recently published in a special issue of The Lancet Diabetes and Endocrinology. Further, on December 8th Dr. Rigby will present the T1DAL 12- and 18-month data at IDS, focusing on the mechanistic findings and their interpretation.
On December 8th at IDS, Steve Gitelman, MD (University of California, San Francisco) will present recently-reported results from the ITN’s START study (Study of Thymoglobulin to Arrest Newly Diagnosed Type 1 Diabetes) which tested antithymocyte globulin (ATG) treatment in type 1 diabetes. In contrast to the T1DAL study, there was evidence of regulatory T cell depletion with preservation of effector memory T cells during the first six months of the study. This unfavorable ratio coincided with a decline in the rate of insulin production, which leveled off during the second six months of the study. This data was also published in the same special issue of The Lancet Diabetes & Endocrinology. In addition to the 12-month data, Dr. Gitelman will also present the 24-month clinical and mechanistic data, which have only just become available and have not been reported previously.
Reflecting on the cumulative findings from these and other studies, Mario Ehlers, MD, PhD (ITN) will give a comprehensive overview of the ITN’s type 1 diabetes portfolio on December 8th at the IDS. Dr. Ehlers will reflect on lessons learned from five completed and ongoing clinical trials in new-onset T1D, including evidence for emerging biomarkers that may be utilized to evaluate treatment responses in future trials. Given the evidence to date, achieving tolerance and permanently reversing disease may require strategic combinations of therapeutics designed to target multiple arms of the immune system to create a favorable environment for tolerance.
Recognizing the promise of combination therapy, the ITN in collaboration with JDRF created the Type 1 Diabetes Preclinical Consortium that conducts preclinical screening of strategic combinations of agents to demonstrate efficacy and enhance mechanistic insight before moving into clinical trials. The consortium consists of four, independent, geographically-diverse laboratories with the goal of generating reproducible data using a single protocol. On December 11th at IDS, Ron Gill, PhD (University of Colorado, Denver), one of the consortium investigators, will discuss the goals and structure of this consortium, as well as present data from the consortium’s two first combination studies: 1) anti-CD20 plus oral insulin, and 2) anti-CD3 plus anti-IL1.
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