Immunology of Diabetes Society : the take-way of May 26th and 27th, 2023.
There are still a few steps to climb before a cure for type 1 diabetes (T1D). Along the way, let's take a look at 4 clinical trials testing different drugs to delay the onset or slow the effects of T1D. Because there's more to diabetes than teplizumab! The diversity of treatments is the strength of prevention. And also of the cure.
PRV-101, the odyssey of a preventive vaccine.
The phases of a clinical trial are a bit like episodes of a saga on the big-screen saga. There's anticipation, action, plot twists and sometimes disappointment in between. Obviously, when this happens in the first episode, the authors have to revise their script.
The second installment in the saga of Provention Bio's PRV-101 vaccine candidate seeks to inactivate type B coxsackieviruses.
To better understand the plot of PRV-101, Professor Pere Santamaria of Proventio Bio reminds us that "coxsackieviruses are among the most widespread viruses. Although they cause generally benign ailments, they can lead to acute infectious diseases, sometimes fatal in newborns. In addition, infection with coxsackie B virus is now considered a key trigger of autoimmunity, including T1D".
Between the administration of three doses and a placebo control group, the plot ran smoothly until the conclusion of a positive Phase II: lasting results six months after the last inoculated dose (for the highest dose), and a trial confirming the generation of antibodies capable of effectively fighting the virus in its various variants.
We'll have to wait for Episode III of the trial to find out whether this scientific work can be made more widely available. We'll then be able to see, in several years' time, whether this preventive film will really have left its mark on a generation of viewers by reducing the number of T1D diagnoses.
Baricitinib for newly diagnosed T1D: the art of keeping the pancreas attention.
Baricitinib has entered the box-office of treatments for people newly diagnosed with an Australian clinical trial. Baricitinib silences cytokines, important proteins in the immune response. Already in use to treat other autoimmune diseases, it is now climbing the steps of the T1D festival, for its second consecutive phase.
After 48 weeks, Barcitinib appears to preserve volunteers' beta cells, reduce insulin doses, lower glycated hemoglobin and increase time on target.
Australian Professor John Wentworth comments: "We still have a long way to go! We need to test the treatment over a longer period. And if we can actually preserve the beta cells, we'll be able to demonstrate to the authorities that prevention makes sense". To do this, we need to confirm the results at other stages of the disease (before and after diagnosis), and combine Baricitinib with other molecules. It will also be necessary to focus on the beta cells of younger patients. A whole program!
Lactococcus Lactis and teplizumab: it's cheese and dessert at the immunology festival buffet.
When all the stars of diabetes immunology gather to share their work, it's safe to assume that the petits fours will match the quality of the speakers. Vegans will no doubt complain, as it is indeed a bacterium derived from cheese that has been used in a tantalizing clinical trial in Belgium.
The recipe is relatively simple! Researchers sought to exploit the intestine to restore the tolerance that would slow down the action of immune cells and leave the pancreas a little in peace. The researchers genetically modified the lactococcus lactis bacterium and turned it into a pill that could be swallowed. All that remained to be done was to wait for the therapy to have a localized effect on the mucous membranes.
The story doesn't say whether the adults and teenagers in the trial enjoyed themselves, but the therapy passed the safety tests. The results obtained in terms of action on the symptoms of T1D are encouraging. Chantal Mathieu, who was involved in the trial, explains: "The level of C-peptide was maintained after eight weeks, and treatment in humans has confirmed the return of the tolerance already observed in mice". Further experiments based on this therapy are considered.
Interleukin-2 in the DIABIL-2 study to delay the onset of type 1 diabetes.
Can low-dose interleukin-2 (IL-2) prevent beta cell destruction? This molecule has been studied for several years by French immunologist David Klatzmann to prevent and delay the onset of T1D. The good news is that IL-2 can prevent and cure T1D in mice. Lucky them! But in humans...
Interleukin-2 is a molecule we produce naturally. At very low doses, IL-2 can stimulate and restore the immune system. It worked for vasculitis, an autoimmune complication of hepatitis C. But for T1D, it's a little more complicated. The DIABIL-2 clinical trial did not produce the expected results. "The molecule had no effect on the 140 patients in the clinical trial," Professor Klatzmann tells with regret to our microphone. But the immunologist is not giving up. "In a new trial, DIAREP-2, I'm attacking the T cells with ciclosporin, a powerful immunosuppressant, for two months to calm the system, then I’m using IL-2 to restore an immune balance." A fight scene followed by a reconciliation scene, that's the secret of a successful film.
Klatzmann's ultimate goal is to prevent diabetes. "For me, IL-2 is at the root of diabetes. If we're able to identify populations at risk, an injection of IL-2 every 15 days would keep these T cells more active".
Immunologist Bart Roep: disRoeptive.
Patients love him, researchers dread him: immunologist and showman Bart Roep isn't afraid to say he's going to cure T1D. In this video, he explains how the immune system of T1D patients fascinates him.
Immunology of Diabetes Society 2023: the end.
From May 23rd to 27th, we tried to cover the major immunology topics of 2023 through daily summary articles and video interviews.
In a nutshell:
- T1D is an autoimmune disease whose onset is established long before diagnosis, which is a late stage.
- The aim of immunology is to successfully treat T1D before diagnosis.
- The large number of treatment ideas and trials are not a matter of scientific dispersion, but the creation of a range of solutions for curing diabetes at all possible stages and in all possible configurations: age, diagnosed or not, typology of infections, antibodies, etc.
No Pancreas Oscar winner this year at the Cannes Festival, but we'd like to reward a number of Hopeful Immunologists of the year for their role in T1D treatment. These are exciting times for T1D research. It's not just talk: we already know and can act in many ways on beta cells and the immune system, but we don't know when T1D will be defeated once and for all. What emerges from our discussions with diabetes experts Roberto Mallone, Mark Atkinson, Bart Roep, Andrea Schietinger, Lucienne Chatenoud, Chantal Mathieu, David Klatzmann, Maran Rewers, Leonard Harrison ... (yes! We met a few celebrities on the diabetes blue carpet!) is that we're going through a change. This can be felt in the content of scientific congress programs and in current and future clinical trials. And whether or not there's a Pancreas Oscar at the end of the film, we at Glucose still feel it's important to convey the various scenes in the film of the cure for T1D. Just like you, we want to see the ending. And above all, we want access to the script!
It's the end of the congress for Glucose toujours!
Youtube: Watch our interviews with leading diabetes immunologists.
Translation: Anna Jones
