Australian Research Features at American Diabetes Association’s (ADA) Scientific Sessions 2018
People with type 1 diabetes (T1D) have to live with it 24 hours a day, 7 days a week, 365 days a year.
But this year’s American Diabetes Association’s (ADA) 78th Scientific Sessions in Orlando, Florida brought hope and inspiration to people living with T1D. The ADA 78th Scientific Sessions highlighted some important JDRF-funded and JDRF-supported research underway, encompassing breakthrough clinical trials and significant research studies that are paving the way to novel and emerging treatments for T1D.
Here are some of the projects showcased at the 78th Scientific Sessions, including some of our very own Australian-based talent:
Australian T1DCRN Career Development Award recipient – a special ADA feature
Of all the incredible global research in the T1D space, we are proud that one of our own, Associate Professor Anandwardhan Hardikar, was part of a select bunch chosen by ADA to feature their research at the conference. A/Prof Hardikar’s research focuses on developing a simple test to detect beta cell death. If successful, a test to measure beta cell loss could significantly accelerate development of therapies to prevent or delay T1D. Watch the video below to find out more.
JDRF’s T1DCRN (Type 1 Diabetes Clinical Research Network) has been supporting A/Prof Hardikar since the Network began, initially with a small grant, and now with a prestigious Career Development Award. JDRF and The Leona M. and Harry B. Helmsley Charitable Trust also partnered to award him a grant. Additionally, A/Prof Hardikar is a current participant in the JDRF/Macquarie Group Foundation Future Research Leaders Program.
SGLT Inhibition – preventing glucose absorption
SLGTs (sodium glucose transport proteins) work by absorbing glucose into the blood from the kidneys and small intestines. The idea is that inhibiting SLGTs using drugs would help to lower blood glucose levels by preventing this absorption.
Sotagliflozin is an investigational dual inhibitor of SGLT proteins 1 and 2 (SGLT1 and SGLT2) that is used for people with type 2 diabetes. The drug has been investigated for use in type 1 diabetes alongside insulin in the ‘inTandem1’ study of 793 adults across 75 US and Canadian sites. The study tested this drug as an additional therapy to insulin.
Dapaglifozin, another investigational dual inhibitor of SGLT2 protein, was tested in more than 800 adults across America, Europe and Asia, in the ‘DEPICT-2’ study.
At ADA Scientific Sessions, dapagliflozin—presented by Paresh Dandona, M.D., and Chantal Mathieu, M.D., PhD.—and sotagliflozin—presented by John Buse, M.D., PhD.—both reduced HbA1c, and also led to a reduction in insulin doses needed and an increased time spent in the recommended blood glucose range. But both showed an increase in diabetic ketoacidosis (DKA), a life-threatening condition caused when insulin levels are too low. Also, DKA did not come with its hallmark symptoms of hyperglycaemia. Fortunately, an additional SGLT-2 inhibitor, empagliflozin (Jardiance®), has demonstrated that in phase III (late stage) trials in adults with T1D, a lower dose of the drug prevented DKA while not compromising on the glycaemic and metabolic benefits.
Clinical trial in beta cell replacement therapy – Viacyte
ViaCyte’s lead candidate for beta cell replacement therapy is the PEC-Encap combination, consisting of pancreatic progenitor cells (PEC-01) encapsulated in a delivery device called the Encaptra® Cell Delivery System. This presentation was the first description of data from the clinical trial that tested the safety and tolerability of PEC-Encap in 19 patients, and the outcomes were very exciting. The results showed that when engraftment occurs — which is when the implanted cells begin to grow new ones — viable mature insulin-expressing islet cells formed. The cells can also live for a long time without the need for immunosuppression. While the study did not show that this combination controlled blood glucose levels, it achieved what it set out to – that the product is safe and feasible for use in people.
JDRF Leadership: JDRF has been funding ViaCyte since 2011, as part of its Industry Discovery and Development Program (IDDP). There are now six companies testing their beta cell replacement therapies through IDDP, with the goal of delivering insulin independence without immunosuppression to the T1D community.
Combination immunotherapy: A clinical trial to preserve insulin production
Findings from a new TrialNet research study show low-dose Thymoglobulin (ATG) slows insulin loss in people newly diagnosed with type 1 diabetes.
Michael Haller, M.D., of the University of Florida, unveiled results of a clinical trial that tested whether a protein and immune activator combination – Thymoglobulin®, or anti-thymocyte globulin (ATG), and Neulasta® known as GCSF – could preserve beta cell function in new-onset T1D. The study found that a short course of low-dose ATG did preserve beta cell function and improved insulin production throughout the entire one-year study period. More so, the people who got ATG or the ATG+GCSF combination had significantly lower HbA1c than people who were given a placebo. These results suggest that ATG, alone or in combination, should be considered as a potential means of slowing T1D progression and preserving beta cell mass. Final findings from this study will be reported in 2019, with more clinical trials to come!
TrialNet is the largest global clinical trial network ever assembled to change the course of type 1 diabetes, The network offers risk screening and innovative clinical studies testing ways to maintain insulin production before and after diagnosis. To get involved in Australia, go to: www.trialnet.org.
JDRF Leadership: Dr Haller received an early career grant from JDRF that provided funding to complete the initial pilot studies of ATG and GCSF in T1D, which laid the groundwork for the larger ATG-GCSF combination trial.
TEDDY Study – The Environmental Determinants of Diabetes in the Young
The TEDDY study aims to identify environmental triggers for T1D, and investigators working on the study provided an update on their findings. Jeffrey Krischer, Ph.D., from the University of South Florida, has results suggesting that T1D is a highly variable but there is a relationship between age of T1D onset, genetics and the type of autoantibodies that appear first. Autoantibodies are proteins produced by the immune system that are directed at the body’s own organs and tissues.
Dr Krischer showed that children who develop islet autoimmunity early tend to develop insulin autoantibodies first and progress faster to T1D, while those who develop islet autoimmunity later in childhood tend to develop autoantibodies to another beta cell related protein called GAD and progress more slowly.
Australia has its own large study investigating environmental triggers of T1D, starting at an earlier stage than the TEDDY study – from pregnancy. To find out more and get involved head to www.endia.org.au. In fact, the Australian ENDIA team also attended the conference to present some research about differences in gut bacteria between those with and without T1D. Further details will be shared when the results are published.
JDRF Leadership: JDRF has supported TEDDY since its inception in 2004, and is currently funding Dr. Krischer for follow-up of children taking part in the study.
New role for neutrophils in T1D
Manuela Battaglia, Ph.D. and her colleagues from TrialNet have found intriguing results regarding the role of a type of immune cell, neutrophils, in the early stages of T1D. TrialNet’s Pathway to Prevention study follows individuals at-risk for T1D and collects samples, allowing investigators to identify triggers and predictors of progression to T1D. Using samples collected by TrialNet, Battaglia has found that there is a reduced number of neutrophils circulating in the blood during progression to T1D. The lower the neutrophil count in an individual, the more likely they are to get T1D and lose beta cell function faster. What’s more, she discovered that neutrophils are abnormal in people who are at-risk of T1D but do not test positive for autoantibodies! Future work will focus on understanding why neutrophils are predictive of T1D and whether targeting neutrophils can slow or stop progression of T1D. Dr Battaglia is a co-investigator on a T1DCRN-funded Innovation Award led by Associate Professor Charmaine Simeonovic in Canberra. They are looking at neutrophils, their interactions with other blood components called platelets, and their role in T1D, in an approach that hasn’t been tested before.
JDRF Leadership: Dr. Battaglia has received JDRF funding since 2008, when she was an early career scientist. She has since received two more grants to study the role that immunological cells can contribute to T1D.
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