At the American Diabetes Association’s Scientific Sessions, which was held virtually from June 25-29, scientists presented on some of the most important topics, from beta cell replacement trials to screening to low blood sugar treatments, all with the same goal: Ending type 1 diabetes (T1D).
Breakthrough T1D played the roles of presenter, educator, and active learner—and was the key funder and supporter of nearly all of the top advances shared in T1D research. There were a number of fantastic results that came through the ADA’s Scientific Sessions. Here are the key Breakthrough T1D takeaways from the conference.
Cures
Pancreatic Precursor Cells Survive, Differentiate, and Produce “Clinically Relevant” Insulin Production
Breakthrough T1D Research Area: Cell Therapies
ViaCyte, a beta cell replacement company, demonstrated that its PEC-Direct therapy helps people with T1D produce insulin again. Data from ViaCyte’s clinical trial show that when pancreatic precursor cells, called “PEC-01™ cells,” are implanted, they are capable of producing circulating C-peptide, a biomarker for insulin production by beta cells, in people with T1D, as well as showing increased time in range, from 54% to 88%; a reduction in HbA1c; and a decrease in average insulin usage, from 39.5 to 27.3 units/day. This is the first time C-peptide has been detected at “clinically relevant” levels, and these data provide unprecedented proof-of-concept that further optimization of PEC-Direct can result in a functional cure for T1D.
Breakthrough T1D Leadership: Breakthrough T1D has been a significant funder of ViaCyte. Early in its history (when ViaCyte was called CyThera), Breakthrough T1D underwrote development of the proprietary line of precursor stem cells used in their treatment. Breakthrough T1D also funded the preclinical and clinical studies of ViaCyte’s PEC-01™ therapies, which are designed to mature into islet tissue in humans, including glucose-responsive insulin-secreting beta cells. This includes the first ever clinical trial to test a stem cell-derived beta cell replacement therapy for T1D, in 2014.
Immune Therapies: HIP to Toes
Breakthrough T1D Research Area: Disease-Modifying Therapies
Immune cells, called T cells, are responsible for T1D. A marker, called an antigen, marks the cell type to be destroyed by the T cells. But how can we use antigens to prevent T cells from attacking beta cells? In the past 10 years, Kathryn Haskins, Ph.D., and Thomas Delong, Ph.D., then a postdoctoral fellow in her lab, discovered a new antigen that makes the T cells strike: Hybrid insulin peptides, or HIPs. (Hybrid, which means it takes part of the insulin molecule and part of another beta cell molecule and links them. Peptide, which is like a protein, but smaller.) What does it mean? HIPs can be used to provide antigen-specific immunosuppression, or ‘tolerance,’ providing protection from developing T1D. Dr. Haskins is using nanoparticles, and Megan Levings, Ph.D., another presenter at the session, is using chimeric antigen receptor (CAR) therapies to induce T cell suppression.
Breakthrough T1D Leadership: Breakthrough T1D has been funding Dr. Haskins since 2000, and funded the postdoctoral work of Dr. Delong, who discovered HIPs. More recently, Breakthrough T1D funded Timothy A. Wiles, Ph.D., a postdoctoral fellow of Dr. Delong, who is developing techniques for analyzing HIPs, which will improve the understanding of the mechanisms underlying T1D and provide targets for antigen-specific strategies aimed at preventing or reversing T1D. Breakthrough T1D is also funding Dr. Levings, for a different project aimed at harmonizing biomarkers of clinical trials testing ustekinumab, an antibody that inhibits two molecules that regulate the immune system. Dr. Levings is also funded by another Breakthrough T1D grant to generate robust stem cell-based therapies for T1D.
General Population Versus Targeted?
Breakthrough T1D Research Area: Screening
Several Breakthrough T1D-funded researchers presented on the current state of screening for T1D-related autoantibodies—antibodies that are directed toward your own body—which can be used as diagnostic tools to identify people at risk. All types of screening—be it general population versus familial—have tremendous upsides, from decreasing diabetic ketoacidosis (DKA)—a complication of T1D due to a shortage of insulin—at the onset of symptoms, preparing for diagnosis, enrolling in clinical trials, and easing the psychologic burden that T1D brings.
Breakthrough T1D Leadership: As a result of decades of Breakthrough T1D-funded research, we can identify those at highest risk for developing T1D—two or more autoantibodies—and we have funded screening programs since they were first introduced in the late 1980s. More recently, Breakthrough T1D has a new initiative, T1Detect, to broaden screening to the general population. The goal: Global universal screening, which is key to developing disease-modifying therapies to keep the disease from progressing and, ultimately, prevent it entirely.
Improving Lives
How to Reduce Low Blood Sugar Events: Smart Insulin and Dual Hormone Artificial Pancreas System
Breakthrough T1D Research Area: Glucose Control
JDRF-funded researchers Danny Chou, Ph.D., and Michael A. Weiss, M.D., Ph.D., MBA, and others are developing glucose-responsive or “smart” insulin, which has tremendous promise for the treatment of T1D. Smart insulins will turn on when they are needed to lower blood sugar, and switch off when blood sugars are in the normal range. In one model, presented at ADA, Dr. Chou’s smart insulin was able to reduce the risk of low blood sugar (called hypoglycemia), even in large doses. In another presentation, Steven J. Russell, M.D., Ph.D., discussed the Beta Bionics iLet Pancreas System. Current and future insulin-only automated insulin delivery (AID) systems have myriad benefits, such as increased time in range, HbA1c reduction, and reduced time spent in high and low blood sugar. One area for improvement is a system that enhances these benefits but also significantly reduces severe hypos—which is a current gap. Beta Bionics dual hormone system—with insulin and glucagon—was able to do so.
Breakthrough T1D Leadership: Breakthrough T1D has been funding Dr. Chou since his postdoctoral days, starting in 2013, when he was at the Massachusetts Institute of Technology, under the mentorship of Breakthrough T1D-funded Robert Langer, Sc.D., and Daniel Anderson, Ph.D. We funded Dr. Weiss from 2017-2020. We funded Dr. Russell from 2013-2016, and Ed Damiano, Ph.D., CEO of Beta Bionics, in 2009-2011, for his early research testing the safety and efficacy of a novel closed loop system that incorporated the use of glucagon in addition to insulin. The results of this work helped to inform the development of the iLet bionic pancreas.
Diabetic Retinal Disease—Changing Before Your Eyes
Breakthrough T1D Research Area: Complications
Jennifer Sun, M.D., MPH, and Thomas Gardner, M.D., M.S., are leading an effort to update the retinopathy staging scale, creating evidence-based recommendations incorporating decades of progress in functional imaging, other biomarkers, and metrics of quality of life.
Breakthrough T1D Leadership: The Early Treatment Diabetic Retinopathy Study (ETDRS) Scale was developed in the 1950s and was limited to point-in-time visual perception. In 2018, Breakthrough T1D launched an ambitious initiative in partnership with the Mary Tyler Moore and S. Robert Levine, MD, Foundation to reverse diabetes-related blindness. As the first step, the inability to adequately monitor the early stages of disease was identified as a key gap to address, and we provided grants to Drs. Sun and Gardner to update the retinopathy scale and staging system. When it’s completed, the improved staging scale will lead to the development of early preventive therapies that will reduce vision-threatening retinopathy progression, and ultimately improving the quality of life for people with T1D.
How Telehealth Can Improve Outcomes in T1D
Breakthrough T1D Research Area: Psychosocial
Many Breakthrough T1D-funded researchers presented on how telehealth can improve outcomes and care for the T1D community, including emergency care, remote monitoring, and digital visits. Telehealth has the potential to dramatically transform access to diabetes care and improve the lives of people with T1D, but different formats will work for different people—no one-size-fits-all approach.
Breakthrough T1D Leadership: Breakthrough T1D is investing in telehealth, funding several grants to study its benefits, measuring psychosocial and glycemic outcomes. In addition, Breakthrough T1D established the National Diabetes Psychology Fellowship Program—the first of its kind. By training psychology professionals to address the needs of people facing T1D, Breakthrough T1D is helping to reduce the significant daily burden of this disease.
Breakthrough T1D CEO Aaron Kowalski, Ph.D., held a virtal happy hour to discuss key takeaways from ADA’s Scientific Sessions. Watch the video below.
