By Noel Morgan, University of Exeter
“Reverse vaccines” could be used to help relieve sufferers of type-1 diabetes from the inconvenience of daily insulin injections. A vaccine usually works by boosting the body’s immune system to fight a certain disease. But in the case of diabetes, which involves the body’s immune system fighting itself, we may need a vaccine that can lower immunity against certain targets.
Type-1 diabetes lasts a lifetime and can have devastating consequences. It occurs when the body ceases to produce sufficient amounts of the hormone insulin to deal with the demand placed on it from the nutrients, particularly sugars, we eat.
The only available therapy for this at the moment is to administer insulin either by injection or via a pump on a daily basis for the rest of the patient’s life. Even then, it is likely that blood glucose levels will fluctuate much more than normal. This can be associated with either hypoglycaemia (when blood glucose levels fall beyond the normal range, leading to impaired brain function) or hyperglycaemia (which, in the long term, can lead to complications such as kidney failure and blindness).
But this new research suggests that vaccinating type-1 diabetes sufferers with specially engineered DNA might help to protect the body’s insulin producing cells.
Cells that search and destroy
The onset of type-1 diabetes often occurs out of the blue and it’s happening to younger and younger patients. Many newly diagnosed cases are in children and while, in the past, the disease occurred most frequently at about the time of puberty, the trend now is for still younger children to develop the illness at an increasing rate.
The reasons for this are unknown but environmental factors may play a role. Among these, it is possible that infection with a virus might either bring on or enhance the progression of the disease. This is important since, if a virus were to be identified as the culprit, this might open the way for a normal vaccination approach.
The underlying pathology of type-1 diabetes is very complex and remains poorly understood. This is mainly because the disease occurs in an inaccessible organ, the pancreas, in patients who usually can go on to live a long and productive life. As a result, the active process has so far been studied in about 170 pancreas samples worldwide in the past century.
Nevertheless, this has shown that the illness is caused by an inappropriate influx of immune cells into the pancreas, resulting in the insulin-producing “beta” cells being selectively targeted and destroyed.
Finding a ‘reverse vaccine’
In a study published in the journal Science Translational Medicine, Bart Roep at Leiden University and colleagues have tested the validity of this concept in a small group of patients with very promising results. They realised that many patients with type-1 diabetes display a common feature: they generate antibodies to certain beta-cell proteins which circulate in the bloodstream. Among these antibodies are those that attack insulin itself. These often appear early in the course of the illness in young children.
So the researchers tested the idea that they could induce a tolerance to insulin by injecting a specially engineered DNA molecule into patients. This molecule carries the code to produce insulin’s precursor, proinsulin, directly inside the muscles of patients.
This would mean that rather than acting as an alternative supply of the hormone, the DNA would allow proinsulin to be produced and to influence the immune system. This could then raise the patient’s tolerance so that the immune cells that kill off the beta cells in the pancreas might be either reduced or eliminated.
These results represent an important step forward but, of course, the work has been undertaken in only a small number of individuals and, as this was a proof of principle study, it was carried out in adult volunteers rather than in children. The treatment period was relatively short and it is not known how long the effect might be sustained.
Nevertheless, the data suggest that the method worked with minimal side effects and was safe. As such, the authors argue that more extensive testing is warranted to establish whether this “reverse vaccine” approach might have more widespread use. If this proves to be the case, they may have hit upon an important means to improve the lives of patients newly diagnosed with type-1 diabetes.
Noel Morgan receives funding from European Union’s Seventh Framework Programme PEVNET (FP7/2007-2013) under grant agreement number 261441. Additional support is from JDRF’s nPOD-V programme, Diabetes UK and the Diabetes Research Wellness Foundation.