In honor of Stress Awareness Month, I’m going to talk about stress…beta cell stress.

You thought that beta cells were passive participants in their own immune-mediated death, leading to type 1 diabetes (T1D)? Wrong.

Researchers in the Network for Pancreatic Organ Donors with Diabetes (nPOD), funded by Breakthrough T1D, found that the beta cells are stressed (something thought to be present in type 2 diabetes, not type 1). Because of this, they become more visible to the immune system and less able to resist inflammatory insults.

What does this mean to us?

Well, scientists could develop therapies that support beta cells and protect them from stress and inflammation, which could help quell the autoimmune response.

It could also help develop new tools for diagnosis, beyond screening for antibodies that are directed at your pancreas (autoantibodies). Let’s say, you get screened, and it tells you that you have 2 autoantibodies. Researchers could develop a test to see if your beta cells were stressed, which may mean that the diagnosis of T1D could happen sooner rather than later.

Learn more about how you can support BreakthroughT1D and their work to prevent, treat, and—one day—find cures for T1D.

The U.S. Food and Drug Administration (FDA) regulatory review is now under way for teplizumab—a therapy that blocks the blood marker CD3, which activates immune cells—to prevent or delay type 1 diabetes (T1D) in at-risk individuals. The target action date is July 2, 2021.

Teplizumab could become the first disease-modifying therapy approved for T1D.

Breakthrough T1D had a hand in the development of teplizumab from nearly the beginning:

Teplizumab, now called PRV-031, is also being tested in a phase III clinical trial in people who have been recently diagnosed, headed by Provention Bio, a company with an investment from the Breakthrough T1D T1D Fund.

If successful, and the FDA review results in approval, we will be moving ever closer to a world without this disease.

Diabetic ketoacidosis (DKA) is scary. It is a major and life-threatening complication due to a shortage of insulin, causing symptoms like dehydration, nausea and vomiting, confusion, difficulty breathing, or even, in extreme cases, coma or death. Approximately 40 to 60 percent of people in the United States present with DKA at the time of type 1 diabetes (T1D) diagnosis.

There is a way to change that, though. It’s called type 1 diabetes screening, and it can identify people at-risk prior to a type 1 diabetes diagnosis.

Breakthrough T1D-funded scientists have discovered that having two or more specific autoantibodies—antibodies that are directed toward your own body or, in the case of T1D, your pancreas—means that you have an almost 100 percent chance of developing T1D.

We can screen for these autoantibodies, and Breakthrough T1D-funded studies have shown that screening followed by close monitoring can help decrease DKA—by a lot—and produce other beneficial health outcomes. It also opens up the opportunity to participate in clinical trials to potentially delay or prevent this disease from occurring at all.

Breakthrough T1D is working to drive new life-changing treatments that can prevent T1D from ever occurring. There are therapies in the pipeline, like teplizumab, that can delay the onset of T1D for nearly three years in people with two or more autoantibodies. This groundbreaking clinical trial, conducted by TrialNet, was the first time we’ve ever been able to delay the onset of T1D in humans.

Some type 1 diabetes screening programs already exist. For example, TrialNet has a screening program, which has been running since 2004. Screening for antibodies in TrialNet is limited to those with a family member, but anyone who tests positive for antibodies may be eligible for a clinical trial.

This means that 85 percent of people who have autoantibodies, but no family history of the disease, are going to develop T1D, and have no idea that they will. What does this mean? It’s time to educate and make screening broadly available to significantly increase the number of people who are screened.

Breakthrough T1D has launched a community-based education and awareness program to expand screening to the general population. The program’s aim is to make people understand what type 1 is, how screening is advantageous to the public, how they can be involved, and what to do if you are positive for autoantibodies.

How You Can Help

If you or someone you know doesn’t have T1D and hasn’t been screened, encourage them to be screened. Go to TrialNet.org for free testing.

  1. Create an account on the screening portal to sign up, see payment options, and order a test kit to be sent to your home.
  2. Provide a few easy, painless blood samples and send your test kit back to the lab.
  3. Receive your autoantibody results, explanations of what they mean, and next steps through your account on the testing website. If you are positive for autoantibodies, you will also receive suggested next steps for reaching out to healthcare providers and educational resources on type 1 diabetes.

If you decide to share your screening results with Breakthrough T1D, you will receive further details on your results. If you are autoantibody-positive, you’ll also be equipped with education on how to monitor for signs and symptoms of T1D or enroll in a clinical trial—either preventive or, once you progress to clinical diabetes, diagnosed.

We hope to screen 5,000 people in the first year. If just one person is autoantibody-positive, and this prevents them from having DKA—and the hospital costs and worry that it brings—we have done our job to improve outcomes and eliminate DKA at diagnosis.

While genetics play a major role in the development of type 1 diabetes (T1D), mounting evidence supports the strong influence of the intestinal environment—called the microbiome—in this disease. Nevertheless, few “microbiome-based” strategies have been tested in clinical trials. Recently, Graciela Lorca, Ph.D., professor of microbiology at the University of Florida, found that one bacterial strain—a probiotic called Lactobacillus johnsonii N6.2—prevented the disease in animal models. Dr. Lorca and Michael Haller, M.D., professor and chief of pediatric endocrinology, went on to test this unique probiotic in healthy adults. Having found that it was safe and associated with promising biomarkers, they developed a current clinical trial to determine the potential for L. johnsonii N6.2 to help children and adolescents with recently diagnosed T1D.

Interest in Microbiome Reset

The trial, available only at the University of Florida, will enroll 57 children and adolescents, ages 8-17 years old, who have been diagnosed with T1D for less than 1 year. Participants will take a capsule containing L. johnsonii N6.2 (or placebo) for 24 weeks, and the researchers will explore the safety and immunological response to the drug. If the study is successful, the results will provide a strong foundation for using L. johnsonii N6.2 in prevention trials in subjects at-risk for T1D.

If you are interested in participating, please contact study coordinator Miriam Cintron, at 352-273-5580 or cintrm@peds.ufl.edu.

Type 1 diabetes (T1D) can be hard to predict in high risk children. Testing for the presence of T1D autoantibodies—antibodies against one’s own proteins—helps reduce the incidence of diabetic ketoacidosis (DKA)—a common occurrence in children upon diagnosis, that can lead to death if not treated—but this testing is not widely available. While having 2 or more T1D autoantibodies is pretty definitive that you will develop T1D, it doesn’t tell you when. Clinical diabetes can follow weeks after your autoantibodies appear, or even decades later.

But what if there was a way to more precisely estimate future T1D risk? Breakthrough T1D-funded scientists in The Environmental Determinants of Diabetes in the Young (TEDDY) study wanted to find out.

They used data from the TEDDY study—of nearly 8,000 high-risk children, followed closely from birth for 9.3 years—to develop a model predicting T1D during the first 10 years of life. They found that three variables were enough—autoantibodies, genetic risk score and family history. The combined risk score, put simply, identifies those children who require frequent surveillance because of the imminent onset of T1D.

This is tremendous for several reasons:

“Using T1D autoantibodies to assess risk and reduce the occurrences of DKA has long been a priority of Breakthrough T1D, and we are working to increase the availability of screening,” says Francis Martin, Ph.D., director of research at Breakthrough T1D. “The work of several members of the TEDDY team has demonstrated that, by including an aspect of genetic testing, you can further target your screening and education to those people who are at the highest risk and need—and is an important area for future research.”

Breakthrough T1D would like to see T1D screening become more readily available, be reimbursed by healthcare providers and become part of early childhood wellness programs. For more information, visit our Early Detection page.

In addition to Breakthrough T1D, the TEDDY study is funded by the National Institute of Health (NIH), as part of the Special Diabetes Program, which has been renewed by Congress numerous times thanks to advocacy and leadership by Breakthrough T1D. The Special Diabetes Program (SDP) is set to expire this year on November 30, and we need your help to urge Congress to renew this critical funding. Through the SDP, the National Institutes of Health (NIH) receives $150 million annually for T1D research. Please encourage supporters to become a Breakthrough T1D Advocate today.

Last year, at the American Association for Diabetes (ADA) Scientific Sessions, a drug, called teplizumab, was able to significantly delay—for over two years—the onset of type 1 diabetes (T1D) in participants with a high risk of developing the disease. This was the first ever study in humans to show a delay in the onset of T1D. But it doesn’t stop there. Breakthrough T1D has updated results, and this is big. The investigators were able to follow up on the individuals who didn’t develop clinical diabetes, and the effect of teplizumab had been sustained: 50% of those treated with teplizumab remain diabetes-free, compared to only 22% of those taking placebo, and the delay in diabetes onset was close to 3 years (35 months). These were presented by Emily Sims, M.D., an assistant professor of pediatrics at Indiana University and a Breakthrough T1D-funded investigator, at ADA’s Scientific Sessions.

Additionally, the participants, both the teplizumab and placebo groups, had a progressive decline in the biomarker that measure’s the body’s ability to produce insulin—C-peptide—preceding the trial. But the teplizumab team found that production of C-peptide actually went up following treatment with teplizumab, especially in the first 6 months after treatment. Like, teplizumab could reverse the downward trajectory of C-peptide loss that was there before the trial.* Um, wow. And there’s more: the increases in C-peptide were correlated with induction of a state of “exhaustion” in “bad” immune cells. Like, they literally took a punch and lost the ammo to keep on attacking the beta cells. Wow (again).

So, could the exhaustion of “bad” immune cells result in not getting T1D or significantly slowing down the time to getting it? Well, we’re not there yet, but we’re close, and closer to a day when T1D might be prevented, forever.

Breakthrough T1D Leadership: Breakthrough T1D funded one of the first clinical trials of this drug, results of which were integral to the teplizumab prevention trial. The study in this report was conducted by TrialNet, a T1D trial consortium funded by NIDDK and by the NIH’s Special Diabetes Program for which Breakthrough T1D is the leading advocate. Multiple studies involving samples and data from teplizumab trials have continued to receive Breakthrough T1D funding. Teplizumab (now called PRV-031) is currently being tested in a phase 3 clinical trial in people recently diagnosed with T1D, headed by Provention Bio, a company with an investment from the Breakthrough T1D T1D Fund. If successful, this could become the first immune therapy approved for T1D.

*In the placebo group, C-peptide still declined.

During a recent Breakthrough T1D Facebook Live event, Jane Buckner, M.D., president of Benaroya Research Institute at Virginia Mason in Seattle, discussed Type 1 Diabetes TrialNet’s Hydroxychloroquine (HCQ) Prevention Study.

“I know a lot of people have questions about Hydroxychloroquine these days,” said Dr. Buckner, co-chair of the study, in acknowledgement of the controversy surrounding HCQ as a potential COVID-19 treatment. “We’re hoping that you can get an understanding for why we’ve chosen to do this clinical trial, how it works and also any concerns related to the use of the medication,” said Dr. Buckner.

During the live event, Dr. Buckner delivered a presentation covering:

Watch the full, recorded livestream:

In this time of great uncertainty, there is some exciting news out of Europe. Innodia, a partnership between public and private entities working together to fund research aimed at biomarker discovery and the prevention of type 1 diabetes (T1D), received an additional €12 million in funding from the European Commission, Breakthrough T1D and the Helmsley Charitable Trust. Led by Breakthrough T1D-funded researcher, Professor Chantal Mathieu, M.D., Ph.D., this funding means this critical project, called Innodia Harvest, can begin.

Innodia began in 2015 as a collaboration between the leading charitable funders of T1D research, Breakthrough T1D, the Helmsley Charitable Trust, The European Commission, and several pharmaceutical companies. In the years since, the consortium has grown to include 40 partners from around Europe and the world.

“Innodia Harvest will build on the success of Innodia and leverage Innodia’s network of clinical trial centers and world-renowned experts to expand on previous biomarker work and conduct clinical trials in close collaboration with people with T1D and family members,” said Jeannette Soderberg, Ph.D., Breakthrough T1D Associate Director, European Research. “In this very important public private partnership, we will be able to test new therapies on large European platform using an EMA endorsed trial protocol, ultimately in the hope to provide the T1D community with a preventive therapy.”

Delaying and preventing the onset of T1D is a key part of Breakthrough T1D’s research portfolio, and identifying biomarkers that indicate T1D in at-risk individuals is paramount to achieving that goal. Innodia Harvest will build on the work that began in 2016 through biomarker validation.

Additionally, this new tranche of funding allows Innodia Harvest to start clinical trials in 2020, bringing preventative therapies one step closer to fruition. These two clinical trials take different approaches to arresting the progression of T1D; one is an immune therapy led by industry and the other is a beta cell therapy driven by academia. This diverse approach exemplifies Breakthrough T1D’s strategy of pursuing several plans of attack to make the biggest impact in the shortest amount of time.

Learn more about the additional funding at the Innodia website.

Credit: Science Advances

Wouldn’t it be nice if you could take a vaccine in infancy, and type 1 diabetes (T1D) would not develop? Preclinical research suggests it might not be that far away.

The viral hypothesis posits that a viral infection may be partly responsible for T1D. The main culprit appears to be coxsackievirus B (CVB)—a common pathogen where, in most circumstances, the infection is asymptomatic or results in mild symptoms. There are no available vaccines that target CVBs. Furthermore, there are six types of CVBs, and different CVB infections cause different diseases. What if you could vaccinate against several CVB types with one vaccine? We could potentially prevent multiple diseases.

Published in Science Advances, researchers—including Breakthrough T1D-funded Heikki Hyöty, Ph.D., and Malin Flodström-Tullberg, Ph.D.—report that a vaccine that they developed against all of the CVB types worked in providing immunity against CVB infections, including protecting against the development of T1D. (It could also help with other CVB-induced diseases, like meningitis, heart inflammation and hand, foot and mouth disease.)

What’s next? The Breakthrough T1D T1D Fund has invested in Provention Bio, which is developing a human vaccine against CVB infection, which could enter clinical trials this year. Such a vaccine could keep a large percentage of the population from developing T1D in the first place. Stay tuned.

You can read more on our plans to make T1D preventable by going here.

Carla Greenbaum, M.D., chair of TrialNet—an international Breakthrough T1D-supported network that is dedicated to finding cures for type 1 diabetes (T1D)—and a professor at Benaroya Research Institute, discussed T1D research in the time of COVID-19, including what TrialNet is up to, on Breakthrough T1D’s Facebook Live event. She chats about:

Watch the full, recorded livestream below: