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, which is part of the research program of the DZD, 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, head of the DZD's research area Type 1 Diabetes and of the Institute of Diabetes Research at Helmholtz Zentrum München, 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
Click here for an author interview with Prof. Ezio Bonifacio.