New clinical study aims to prevent type 1 diabetes in children

SINT1A is led by Helmholtz Zentrum Muenchen, and part of the international GPPAD initiative including Prof. Ezio Bonifacio and his team at the Center for Regenerative Therapies Dresden at TU Dresden.

Around one in 300 children and adolescents are diagnosed with the autoimmune disease type 1 diabetes by 18 years of age. Around 90 percent of patients do not have a close relative with type 1 diabetes, meaning the disease can affect any child without a disease history in their family. People with type 1 diabetes must inject the hormone insulin for the rest of their lives because their own immune system is attacking the insulin-producing cells in the “islets” of their pancreas. Insulin has a vital function, transporting sugar from the blood into the body’s cells. The body’s own insulin is often the first target of the immune reaction which leads to type 1 diabetes.

Improving the immune system with probiotics
In early stages of type 1 diabetes, so-called islet autoantibodies appear in the blood as a result of the immune system attacking the insulin-producing cells. Researchers know from earlier studies that children who develop these antibodies can suffer from imbalances in their intestinal flora in early childhood. The new SINT1A (Supplementation with B. Infantis for Mitigation of Type 1 Diabetes Autoimmunity) study aims to prevent the occurrence of islet autoantibodies in children with an increased genetic of type 1 diabetes risk by administering a probiotic containing a strain of Bifidobacterium Infantis (activated B. infantis EVC001) together with their daily nutrition. This is hypothesized to promote a healthy and balanced development of the intestinal flora, which is thought to have beneficial effects on the immune system before the first signs of autoimmunity appear.

SINT1A follows the ongoing Primary Oral Insulin Trial (POInT), which administers insulin orally to train and sensitize the immune system at an early stage so that autoimmunity against insulin does not occur. “We believe that the immune system of the oral and gut mucosa is very important for preventing immune-mediated diseases like type 1 diabetes. The POInT study uses the gut (where the oral insulin arrives) to familiarize the immune system with insulin and prevent an autoimmune response against it. SINT1A was designed based on the knowledge that a healthy gut microflora reduces inflammation and this helps the immune system better distinguish antigens that are safe from those that are dangerous” explains Prof. Bonifacio, study leader in Dresden. In this way, the SINT1A investigators want to reduce the chances that children with a high genetic risk of developing type 1 diabetes start immune responses that lead to autoimmunity. “If the results for both studies show what we are hoping for” explains Prof. Bonifacio “we will aim to combine both studies for an optimized synergistic type 1 diabetes prevention strategy. Type 1 diabetes could be transformed from a previously unavoidable fate into a disease that can be prevented.”

The SINT1A study will start in April 2021 in multiple European countries as part of GPPAD (Global Platform for the Prevention of Autoimmune Diabetes) – an international initiative to prevent type 1 diabetes. The GPPAD research sites are located in Belgium (Leuven), Germany (Dresden, Hanover, Munich), Poland (Warsaw), Sweden (Malmoe) and the UK (Cambridge, Newcastle).

Newborn screening for type 1 diabetes risk
Participation in the SINT1A and POInT studies require proof of an increased genetic type 1 diabetes risk. Newborn screenings allow detecting this risk long before the disease manifestation. The test can be performed with a few drops of blood within the first 7 days of life. Prof. Bonifacio and his team launched a newborn screening program for this purpose in 2016 (which goes by the name ‘Freder1k’ in Germany). “Together with the strong scientific network of GPPAD, we have been able to examine 245,000 babies in international newborn screenings. In 1.15 percent, we found an increased genetic risk. Early detection is imperative for taking meaningful preventive measures,” says Prof. Reinhard Berner director of the children hospital.

Research to prevent type 1 diabetes

The Leona M. and Harry B. Helmsley Charitable Trust is funding the new SINT1A study and the continuation of the established newborn screening with more than US$30 million. “At Helmsley, we are committed to investing in bold ideas,” says Dr. Anne Koralova, a Program Officer at Helmsley. “GPPAD is one of our largest investments because it holds so much promise and represents the kind of international collaboration needed for scientific breakthroughs.”

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Ezio Bonifacio is Professor at the Medical Faculty and Center for Regenerative Therapies Dresden (CRTD) at the TU Dresden, Germany.

Prof. Reinhard Berner is Director of the Childrens Hospital Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

More information about Sint1a

In order to take part in the SINT1A study, children may not be older than six weeks. Half of the SINT1A participants will receive Bifidobacterium Infantis (B. infantis EVC001) and half will receive a placebo. Parents can enroll their children without charge at a GPPAD testing center. Learn more about the GPPAD testing centers: https://www.gppad.org/en/sites/

About all studies

SINT1A, POInT and the newborn screening study are part of GPPAD. The GPPAD studies are led by Helmholtz Zentrum Muenchen. All data generated in the GPPAD studies aim to serve scientific progress that might eventually benefit patients. Therefore, GPPAD makes pseudonymized data and samples from the biobank available to the scientific community upon request. Learn more about GPPAD data sharing:
https://www.gppad.org/en/data-sharing/

All GPPAD studies at a glance:
https://www.gppad.org/en