In partnership with The France Foundation, AAI has introduced a CME activity on the autoimmune science of type 1 diabetes (T1D). “The New Story of T1D: Autoimmune Science Meets Clinical Action” provides a maximum 1.5 AMA PRA Category 1 Credits™ and prepares clinicians to identify opportunities for early intervention in T1D treatment. We asked the faculty about the course and why clinicians need to understand the autoimmune nature of T1D.
Joshua Vieth, PhD, is Senior Director of Research at Breakthrough T1Dand leads the disease-modifying therapies team and portfolio. Mark Anderson, MD, PhD, is A.W. and Mary Margaret Clausen Distinguished Professor in Metabolism and Endocrinology and Robert B. Friend and Michelle M. Friend Endowed Chair in Diabetes Research at the University of California, San Francisco.
AAI: How does understanding T1D as an autoimmune disease improve patient outcomes?
VIETH: T1D starts years before someone needs insulin. The immune system gradually destroys the insulin-producing beta cells, and we can detect that process early through islet-specific autoantibodies.
Focusing on T1D as an autoimmune disease with defined stages, the ability to screen and monitor, and an availability of disease-modifying therapies that target the underlying autoimmune pathobiology moves beyond what has been the traditional paradigm of treating the metabolic symptoms. This is a monumental shift in how clinicians can approach T1D, and an ability to identify and intervene for individuals before symptoms.
This translates to reduced instances of life-threatening diabetic ketoacidosis at diagnosis, fewer adults misdiagnosed with T2D, and an opportunity for individuals to consider their therapeutic options before advancing to lifelong insulin replacement therapy.
ANDERSON: There are several reasons for this. First, autoimmune diseases frequently don’t happen in isolation as a single disease. Patients with T1D are at increased risk for other autoimmune diseases like Hashimoto’s thyroiditis, autoimmune gastritis, vitiligo and Addison’s disease. Thus, screening and awareness for these complications is important.
Second is the recent approvals of Teplizumab (anti-CD3) for the treatment of new onset T1D and for the prevention of T1D in patients with stage 2 diabetes. In the case of the latter, these interventions frequently lead to prolonged c-peptide preservation and better control of T1D.
AAI: What is the most important recent discovery about T1D and the immune system?
ANDERSON: This is hard to pinpoint to a single discovery as there are many interesting developments. For example, we have come to appreciate that a small fraction of patients being treated with cancer immunotherapy are developing T1D as a side effect, particularly if the drug targets PD1. This gives us a new avenue to understand how tolerance to pancreatic islets is maintained.
Meanwhile, this past year the awarding of a Nobel Prize for the discovery of Tregs. Interestingly, patients with mutations in FOXP3, the master regulator of Tregs, often develop T1D. These clues into the major switches that immune tolerance is using to prevent T1D provide us clues on who to halt the autoimmune process in T1D.
VIETH: For me, it’s clinical proof that we can change the course of T1D by targeting the immune system. Teplizumab, the first disease-modifying therapy for T1D, can delay the onset of symptomatic stage 3 T1D (clinical diagnosis). Combine that with an increasing ability to identify people years in advance through autoantibody screening, and there a real window for intervention that didn’t exist a year ago.
AAI: What do you think is on the horizon for T1D treatment?
VIETH: I’m extremely optimistic about the next few years of advancements in the field. Progress toward the development of cures for T1D is happening on three different fronts.
The first is early detection, so we find more people sooner and in their progression. The second is disease-modifying therapies, including the development of combinations that address both the autoimmunity and support or expand someone’s own beta cells. Several immune therapies, some already approved for other indications, have shown they can help preserve a person’s own insulin production.
We also know that preserving insulin function is an important factor in reducing long-term complications related to T1D. As we expand the clinical trial infrastructure and improve clinical efficiencies around recruitment and clinical endpoints, an extremely robust pipeline of potential therapies comes into focus.
The third front is beta cell replacement therapies. Stem-cell derived islets have already allowed some trial participants to stop taking insulin. The next step is doing this with less severe immunosuppression, or through approaches such as gene-editing that may remove the need for immunosuppression altogether.
It’s important to note that immunology is central to all three fronts, which is I why I’m so glad AAI is bringing this course to its membership. The engagement of immunologists is a critical component in the development of the next generation of therapies and cures for T1D.
ANDERSON: There is a lot of excitement about beta cell replacement with stem cell-derived beta cells, and this is a major achievement. This sets the stage for advances in how to both manipulate and shield those cells from immune rejection and also to get new clinical trials going so that beta cell replacement can happen with a treatment that confers lasting immune tolerance to those cells. In the case of the latter, much more work needs to be done, but it will be a huge opportunity for new approaches to immune tolerance.
Source: news.aai.org
