The objective of the next phase of testing will be to determine whether an insulin vaccine can prevent the outbreak of the disease over the longer term.
Children with type 1 diabetes require several insulin injections every day of their lives. This is because the body’s own immune system destroys the beta cells in the pancreas – the cells that produce insulin. This is a process that starts early. Instead of ignoring proteins such as insulin, the immune defences see insulin and other proteins in the cells as foreign and mobilize immune cells to destroy the beta cells. Normally, the immune system develops an immune tolerance to the body’s own proteins during the first years of life, thus preventing this type of autoimmune response. This tolerance includes the training of immune cells that prevent destruction of the body’s own cells. The aim of the insulin vaccine is to help “train” this positive preventive immune response.
In the Pre-POINT study, children at high risk for developing type 1 diabetes in Germany, Austria, the United States and the United Kingdom were treated with oral insulin once daily over periods averaging half a year. The control group was given only a placebo with no effect. The active substance group ingested the insulin in powder form together with food at varying dosage levels that were increased in the course of the study. In the highest dosage (67.5 mg), the insulin powder then induced the desired immune response. Professor Ezio Bonifacio from the Center for Regenerative Therapies, who acted as the Principal Investigator for the study, commented on the results as follow: “…we were pleased to see that there were no unwanted side effects and thus far only signs that we could mimic what normally happens in children who don’t get type 1 diabetes.” Since insulin in this dosage form is broken down in the stomach it did not influence blood glucose levels. “…we believe that most of the response is happening while insulin is still in the mouth“, Bonifacio added.
In the opinion of Prof. Anette-Gabriele Ziegler from the Institute of Diabetes Research, which also contributed to the study, the unique thing about this double-blind study is that the insulin was administered as a prophylactic vaccine to the children before they had developed an autoimmune response – that is before they produced autoantibodies. Ziegler continued: “This is a revolutionary way to prevent type 1 diabetes, but it is quite logical that if the body’s immune system doesn’t learn how to make the protective responses by itself, we need to give it a little help.“
The JDRF (Juvenile Diabetes Research Foundation) in the US, which provided supportive funding for the project, assessed the study results in a positive light: “The JDRF is very encouraged by the results of the Pre-POINT study as a first step to potentially prevent type 1 diabetes in children that are at high risk for getting T1D,” said Julia Greenstein, JDRF Vice President of Discovery Research. “This is a significant finding and given JDRF’s mission to achieve a world without type 1 diabetes, these study results are exciting and bring us one step closer to the potential of seeing an oral vaccination strategy to prevent this disease.“
In follow-up studies, treatment will be given to a larger number of babies who are genetically at risk for type 1 diabetes. If the vaccine then succeeds in preventing the disease over the longer term, this would open the door to blanket coverage with the preventive vaccine.
Bonifacio, E. et al. (2015): Effects of High-Dose Oral Insulin on Immune Responses in Children at High Risk for Type 1 Diabetes. The Pre-POINT Randomized Clinical Trial. JAMA 2015; 313(15):1-10. doi:10.1001/jama.2015.2928
The CRTD was founded as an interdisciplinary, tightly integrated network of 17 research groups in the core centre and over 75 full members at seven different research institutes in Dresden. Seven professors and ten research group heads are currently doing research at the CRTD. The members of the CRTD network work, for instance, at the Biotechnologisches Zentrum (Biotechnology Centre) of the TU Dresden, the Max-Planck-Institut für molekulare Zellbiologie und Genetik (Max Plank Institute for Molecular Cytobiology and Genetics), the Max-Bergmann-Zentrum für Biomaterialien (Max Bergmann Centre for Biomaterials), the “Carl Gustav Carus” University Clinics or on the medical faculty of the TU Dresden. 8 scientific partners also provide support to the CRTD network, which bundles the scientific expertise to facilitate rapid and efficient development of innovative regenerative treatments.
As the German Research Center for Environmental Health, the Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of common major diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in northern Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centres with a total of about 31,000 staff members. www.helmholtz-muenchen.de
The Institute of Diabetes Research (IDF) focuses on the origins and prevention of type 1 as well as type 2 diabetes as a late sequel of gestation diabetes. Development of an insulin vaccine to prevent type 1 diabetes is a high-priority project at the institute. In large-scale, long-term studies, the IDF is studying the interrelationships of genetics, environmental factors and the immune system with the pathogenesis of type 1 diabetes. Using the data on the birth cohort BABYDIAB, established in 1989 as the first prospective diabetic birth cohort worldwide, both high-risk genes and antibody profiles can be identified. Based on these data, predictions of development and outbreak of type 1 diabetes are possible that will alter both the classification and time of diagnosis of the disease. The IDF is part of the Helmholtz Diabetes Center (HDC).
For further information on the publication:
CRTD / DFG-Center for Regenerative Therapies Dresden – Cluster of Excellence / TU Dresden, Fetscherstraße 105, 01307 Dresden
Tel. +49 351-458 82-101, E-Mail: info(at)crt-dresden.de
For no-obligation information on preventive vaccination studies:
Institut für Diabetesforschung, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 München
Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Lehrstuhl für Diabetes und Gestationsdiabetes der Technischen Universität München
Univ.-Prof. Dr. med. Anette-Gabriele Ziegler
Kölner Platz 1, 80804 München
Tel. +49 800 – 828 48 68 (toll-free)
E-mail: [email protected]
For further information on the Pre-POINT study go to: