At ADA, JDRF-Funded Research Takes Center Stage (with a “Happy Hour” by Dr. Aaron Kowalski)

in , , ,

ADA Scientific Sessions June 3-7, 2022

At the American Diabetes Association’s 82nd Scientific Sessions, which was held in person (as well as virtually) from June 3-7, scientists presented on some of the most important topics, from stem cell-derived cell replacement trials to type 1 diabetes (T1D) screening to artificial pancreas technologies, all with the same goal: Ending T1D.

JDRF played the roles of presenter, educator, and active learner—and was the key funder and supporter of nearly all the top advances shared in T1D research. There were many fantastic results that came through the ADA’s Scientific Sessions. Here is Aaron J. Kowalski, Ph.D., CEO of JDRF, with the key takeaways from the conference, and there is a written summary of JDRF highlights below.

You can view all of the oral and poster presentations on the Diabetes journal website.

Cures

Stem Cell-Derived Beta Cell Therapy: Advancing Clinical Trials

JDRF Research Area: Cell Therapies
Cell replacement therapies, including stem cell-derived islet therapy, were on fire, with Vertex Pharmaceuticals and ViaCyte leading the way in clinical trials. Vertex launched its clinical trial of VX-880, a stem cell-derived beta cell therapy in T1D, in combination with immunosuppressive therapy to protect the cells from rejection, in the summer of 2021. To date, three participants have received the drug, and one is now insulin independent! ViaCyte, in partnership with CRISPR Therapeutics, initiated its first-in-human gene-edited, stem cell replacement therapy, without immunosuppression, called VCTX210.

JDRF Leadership: Vertex’s VX-880 therapy was pioneered by Doug Melton, Ph.D.—who moved from Harvard to Vertex Pharmaceuticals to work on their stem cell-derived cell replacement therapies—after successfully transforming stem cells into beta cells in 2014. Another pioneer in cell replacement therapies for T1D is Timothy Kieffer, Ph.D., who also recently moved from the University of British Columbia to serve as Chief Scientific Officer at ViaCyte. They had JDRF funding from 2000 on.

We also heard from Sernova, who provided an update on the phase I/II clinical trial of their Cell Pouch™—an implantable device designed to form a natural environment and allow the survival and function of insulin-producing (islet) cells. The first three individuals to receive the therapy into the Cell Pouch™, with a supplemental marginal dose of islet cells via the portal vein, have been insulin independent for 2 years, 6 months, and 3 months, respectively. JDRF continues to support Sernova to make their Cell Pouch part of the cure portfolio.

Meeting attendees also heard clinical and preclinical data updates from several investigations on encapsulation and immune-tolerance strategies to protect transplanted islet cells from the immune system, featuring a world-renowned set of T1D researchers, including JDRF-funded James Shapiro, M.D., Ph.D. (who is known for his leadership on the Edmonton Protocol), and Andrew R. Pepper, Ph.D., of the University of Alberta, Canada, Bernhard Hering, M.D., from the University of Minnesota, and José Oberholzer, M.D., of the University of Virginia.

Immune Mechanisms of T1D: Innate Versus Adaptive Immunity…or Both

JDRF Research Area: Disease-Modifying Therapies
Adaptive immune cells are responsible for T1D, but beta cell stress and dysfunction precede this onslaught, with innate immune cells taking charge. It turns out that the prohormone to islet amyloid polypeptide (proIAPP, for short)—as C. Bruce Verchere, Ph.D., and Rebecca Hull-Meichle, Ph.D., discussed in their presentations—is elevated prior to clinical diagnosis, in addition to proinsulin—the precursor to insulin. proIAPP, in turn, sparks inflammation and innate immune cell damage. Dr. Verchere has developed a test to measure two kinds of proIAPP in humans, which, ultimately, will provide new insight into the immune cell types and immune mechanisms leading to beta cell function and pave the way for new therapies and biomarkers of beta cell stress.

JDRF Leadership: Dr. Verchere received a JDRF postdoctoral fellowship beginning in 1992 and Dr. Hull-Meichle received one in 2001-2003. The titles, respectively: “Role of Islet Amyloid Polypeptide in Normal and Abnormal Islet Function” and “The Role of Islet Amyloid Formation in Diabetes.” More recently, Heather Denroche, Ph.D., who Dr. Verchere credits in his presentation, received a JDRF postdoctoral fellowship from 2014-2017 and an advanced postdoctoral fellowship from 2018-2022.

“JDRF’s support has been instrumental to my development as a scientist and allowed me to make valuable contributions to type 1 diabetes research….I am truly grateful for this experience.”

– Heather Denroche, Ph.D.
Director, Preclinical Development
Integrated Nanotherapeutics

Dr. Verchere is now leading the JDRF Center of Excellence at the University of British Columbia, where he is working on immune and beta cell therapies, including stem cell-derived therapies, with Dr. Kieffer; James Johnson, Ph.D., who received a JDRF Career Development Award in 2005-2010; Francis Lynn, Ph.D., who was a JDRF postdoc from 2004-2006, advanced postdoc from 2007-2009, and a JDRF Alan Permutt Career Investigator from 2012-2016; and Megan Levings, Ph.D., who has received two JDRF grants since 2015 and has been a mentor to two JDRF postdocs.

General Population Screening: It’s Time

JDRF Research Area: Screening
Several JDRF-funded researchers presented on the current state of screening for genetic risk and/or T1D-related autoantibodies—antibodies that are directed toward your own body. Chantal Mathieu, M.D., Ph.D., gave a spirited talk about why it’s time to screen for T1D in the general population. The first point: T1D is a serious and important health problem and we have learned a lot from family screening and prevention studies. The second point: Decreasing diabetic ketoacidosis (DKA)—a complication of T1D due to a shortage of insulin levels in the body—should be, in itself, enough to warrant population screening. Post-screening, we must be ready with follow-up and guidance so families know what to do with autoantibody status, including clinical trials, like teplizumab—and screening will help identify populations who can benefit from them.

“100 years after the development of insulin, we still have people dying from DKA in all of our countries.”

– Chantal Mathieu, M.D., Ph.D.
KU Leuven, Belgium
Coordinator, INNODIA

JDRF Leadership: As a result of decades of JDRF-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, JDRF 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

From the DIY System and Klue to the Omnipod 5 and the iLet Bionic Pancreas

JDRF Research Area: Artificial Pancreas
A ton of presentations focused on the artificial pancreas, or automated insulin delivery (AID), systems. The first: Results from the first randomized clinical trial testing a do-it-yourself, or DIY, open-source, community-built AID technology, using the OpenAPS algorithm plus the DANA or YpsoPump insulin pump and the Dexcom G6 continuous glucose monitor (CGM). The study included 100 children and adults in New Zealand who used the DIY system compared to those without the algorithm, headed by JDRF grantees Martin de Bock, Ph.D. (who also gave the presentation), and Dana Lewis, the founder of the DIY artificial pancreas system movement. There was no severe hypoglycemia and no DKA and more participants achieved time-in-range of ˃70% using the OpenAPS algorithm, especially at night: Conclusion: The open-source AID was safe and effective in T1D compared to those without the algorithm.

Next up: Researchers presented results from a novel closed loop system that eliminates manual mealtime bolusing. Medtronic teamed up with Klue, an Apple-watch based application that detects eating hand gestures, to see if it could provide a “handsfree” artificial pancreas system. The system converted hand gestures to carb amounts and automatically bolused via a Medtronic 780G pump, and there was no significant difference in time-in-range achieved with this system compared to when participants bolused manually. By eliminating the burden of carb-counting, this system may improve the quality of life in persons with T1D without sacrificing glycemic outcomes.

Next: Omnipod 5, a tubeless hybrid closed loop system, in preschool children. Presenting on this was Daniel DeSalvo, M.D., who had a JDRF postdoctoral fellowship from 2014-2016, with world-renowned researcher Bruce Buckingham, M.D. This was an extension study, to evaluate if glycemic outcomes continued at 12 months (compared to the 3 months in the pivotal trial), and they did! At 12 months, these children had lower A1c and greater time-in-range, and there was no DKA or severe hypoglycemia, indicating the potential long-term benefit of the Omnipod 5 in very young children with T1D. The Omnipod 5 is under FDA review for ages 2-5 years; let’s hope this study will resolve any fears that the AID system is not warranted in preschool aged children.

And finally, the results from the randomized insulin-only iLet bionic pancreas pivotal trial. These were presented by Steven Russell, M.D., Ph.D., at the Advanced Technologies & Treatments for Diabetes (ATTD) conference in April 2022, but now we have patient reported outcomes, presented by Jill Weissberg-Benchell, Ph.D., a professor at the Ann & Robert H. Lurie Children’s Hospital of Chicago, who discussed adults, with many reporting decreased distress, with less worry, guilt, and burnout due to increased time-in-range and no need to carbohydrate count, and youth, who reported positive experiences, including improved A1c, increased independence, and less time managing diabetes.

JDRF Leadership: Dr. Russell received a JDRF grant from 2013-2016 to refine the iLet pancreas, based upon the work of Ed Damiano, Ph.D., CEO of Beta Bionics, who JDRF funded from 2009-2011, for his early research testing the safety and efficacy of a novel closed-loop system (including Firas El-Khatib, Ph.D., a JDRF postdoctoral fellow in his lab). The results of this work helped to inform the development of the iLet bionic pancreas.

Diabetic Retinal Disease—Changing Before Your Eyes

JDRF Research Area: Complications
Sobha Sivaprasad, M.D., reported on The Restoring Vision Moonshot, a “really radical” approach to end diabetic eye disease. The Early Treatment Diabetic Retinopathy Study (ETDRS) Scale, which is used to assess progression of retinopathy, was developed in the 1950s and was limited to point-in-time visual perception, but Dr. Sivaprasad is part of 50 global experts, who will review the literature on diabetic eye disease “in the next year,” and come up with an evidence-based updated retinopathy staging scale, creating recommendations incorporating decades of progress in functional imaging, other biomarkers, and metrics of quality of life. When it’s completed, the improved staging scale will lead to the development of early preventive therapies that will reduce vison-threatening retinopathy progression, and ultimately improving the quality of life for people with T1D.

JDRF Leadership: JDRF has supported eye disease research since its beginning, and has driven discoveries that have reduced the risk of blindness by 95 percent, including laser therapy and anti-VEGF treatments. In 2018, JDRF and the Mary Tyler Moore and S. Robert Levine, MD, Foundation launched the Restoring Vision Moonshot, an ambitious initiative to reverse diabetes-related blindness and vision-threatening eye disease, which afflicts millions of individuals worldwide, held in honor of Mary Tyler Moore’s contributions to diabetes awareness and research.

Improving Health Equity in T1D

JDRF Research Area: Psychosocial
Many JDRF-funded researchers presented on psychosocial issues, including the stigma associated with diabetes, suicide and self-harm, and social inequities—economically vulnerable, minorities, food insecurity—in diabetes care. Specifically, Shivani Agarwal, M.D., M.P.H., and Jeffrey Gonzalez, Ph.D., who have a new grant from JDRF to evaluate telehealth in minority children and teens, and David V. Wagner, Ph.D., who had a JDRF advanced postdoctoral fellowship from 2000-2003 and a number of JDRF grants since, spoke to the many populations who experience poor outcomes in T1D and how they can be addressed. There is a lot of work to be done to improve outcomes for all people with T1D, both in the United States and around the world, but JDRF is committed to helping reduce the significant daily burden of this disease and, ultimately, improve health outcomes for the entire T1D community.

You can view all of the oral and poster presentations on the Diabetes journal website.