This year’s American Diabetes Association’s (ADA) Scientific Sessions in Orlando, Florida highlighted some important JDRF-supported research underway, encompassing breakthrough clinical trials and significant research findings that are paving the way to novel and emerging treatments for T1D.
Some of the projects showcased at ADA Scientific Sessions 2018 are highlighted below:
Australian T1DCRN Career Development Award recipient featured research
We are proud that one of our own, Associate Professor Anandwardhan Hardikar, was part of a select few researchers chosen by ADA to feature their research at the conference. A/Prof Hardikar’s research focuses on developing a detection kit using a biomarker signature to detect beta cell death. Currently, diagnosis of T1D occurs only after 70-80% of beta cells are destroyed. If successful, a test to measure beta cell loss could significantly accelerate development of therapies to prevent or delay T1D and serve as a potential population screening method for T1D. Click the below link to watch the video screened at ADA.
The T1DCRN has been supporting A/Prof Hardikar since the Network began, initially with a seed grant, and now with a prestigious Career Development Award (CDA). 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 findings
SGLT (sodium glucose transport proteins) absorb glucose into the blood from the kidneys and small intestines. Inhibiting this process lowers blood glucose levels.
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 inTandem1 study, a double-blind, phase 3 trial conducted at 75 sites in the U.S. and Canada in 793 adults with T1D, compared the safety and efficacy of two different doses of oral sotagliflozin—each used in addition to optimised insulin—to optimised insulin alone. The results were published in Diabetes Care.
Dapaglifozin, another investigational dual inhibitor of the SGLT2 protein, was tested in more than 800 adults across North and South America, Europe and Asia, in the ‘DEPICT-2’ study. DEPICT-2 was a phase 3, double-blind, global study conducted among 137 sites in North America, South America, Europe and Asia to evaluate the efficacy and safety of dapagliflozin as an add-on to insulin therapy in people with T1D.
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). 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 trials in adults with T1D, a lower dose of the drug prevented DKA while not compromising on the glycaemic and metabolic benefits. Patient and clinician education will be key to bringing these drugs to people living with T1D.
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, viable mature insulin-expressing islet cells formed. The cells can also live for time without the need for immunosuppression. The trial achieved its primary outcomes of safety and tolerability.
Combination immunotherapy to preserve insulin production
Michael Haller, M.D., of the University of Florida, unveiled results of a clinical trial that tested whether 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 took 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.
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 find out more about TrialNet in Australia, go to: www.trialnet.org.
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 heterogenous disease but there is a relationship between age of T1D onset, genetics and the type of autoantibodies that appear first.
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 GAD autoantibodies, 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 head to www.endia.org.au. In fact, the Australian ENDIA team also attended the conference to present some research about differences in the gut microbiota between those with and without T1D. Further details will be shared when the results are published.
Novel role for neutrophils in T1D
Manuela Battaglia, Ph.D. and her colleagues from TrialNet have found intriguing results regarding 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. Additionally, she discovered that neutrophils function abnormally 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.