MEDICAL RESEARCH
   Type 1: Towards new therapies?

What is the initial cause of juvenile diabetes? Why are Finnish children, more than any other young people in the EU, affected by Type 1 diabetes? Various different European research projects are devoted to obtaining a greater understanding of this illness and its early diagnosis based on genetic factors.

Research into the marker known as PDX1, which acts as a transcription factor for an insulin gene, is one of the areas covered by the “EuroStemCell” project. In the image above, the darker spots that appear in green show, on the left, the development of pancreatic cells. On the right, the image shows insulin-producing beta cells at a mature stage of development. Studies on these beta cells, aimed at finding new therapies for the regeneration of the pancreas, are the subject of cooperation with the researchers in the parallel European project “BetaCellTherapy” (see EuroStemCell).

The viral route
The molecular manifestations of Type 1 diabetes are being studied by the 28 centres in the Toneca coordination network with the aim of finding drugs capable of stopping this malfunctioning. The researchers suspect that certain viral infections that only emerge against a given genetic background may be responsible for triggering the disease. Harmless to most children, these infections trigger an autoimmune process whereby the insulin-producing cells in the pancreas of some children are destroyed. Finland, Sardinia and Sweden have the highest incidence rates for Type 1 diabetes in the world, the reason for which remains a mystery to the researchers. The “Viruses in Diabetes” project was set up to test the hypothesis that the enterovirus played a role. The partners in the project focused on 250 children (Finnish, English, Swedish and Greek) suffering from Type 1 diabetes with a control group of 250 additional children. The Eurothymaïde consortium is studying, in particular, how viral infections can induce this type of diabetes in individuals who have the right combination of genes to predispose them to the condition. An infection caused by these enteroviruses would normally go unnoticed, but could be the trigger in these children. If a definite link is identified, it will be possible to develop an antiviral vaccine to protect this group of children from Type 1 diabetes.

From cell grafts…
While waiting for a means of detecting the disease at an early stage, other work is focusing on regenerative approaches with the aim of reconstructing the pancreas. For about ten years now, pancreatic cell grafts have proved effective, but are still reserved for the most serious cases due to a lack of graft donors. As Olle Korgsen, from Uppsala University Clinic in Sweden and Coordinator of the European Consortium for Islet Transplantation, explains, “the five Belgian, Italian, German, Swedish and Dutch centres in our consortium can only carry out about fifty transplants per year.” This is why it is so important that procedures are standardised and the clinical results of these grafts are shared to guarantee the best possible scientific practice.

However useful they may be, grafts are not set to become a routine treatment. Each case requires long-term therapy with immunosuppressants to ensure the cells are not rejected. The patient’s dependence on injections of immunosuppressants is then more or less just a matter of replacing a previous dependence on insulin. An attempt to break out of this vicious circle is precisely the reason that the ‘Riset’ integrated project is studying ways of improving the body’s tolerance of the graft.

…to stem cells
Two further promising alternatives to grafts are also being studied by European researchers. The first, developed by the BARP+ (BioArtificial Pancreas) consortium, relates to the development of an artificial pancreas, the aim being to encapsulate the grafted cells in an artificial biomaterial that allows the insulin to pass through but protects the cells from the defence mechanisms of the body’s immune system. The second alternative, which is even more ambitious, aims at reconstructing the pancreas using stem cells – adult and embryonic stem cells that can reproduce to create identical cells but that can also differentiate into the desired cell type. The “EuroStemCell” consortium is exploring this promising avenue, even though fundamental research is required before the transition to clinical trials can be made.