Bloggers: Arne Kristian Sandvik og Jan Kristian Damås
For patients with these diseases, and for the health professionals who are involved in their treatment, this question seems misplaced. However, many others perceive these to be rare conditions, and a marginal medical problem.
Chronic intestinal inflammation consists of ulcerative colitis and Crohn’s disease. An international abbreviation for these diseases is IBD, which stands for Inflammatory Bowel Disease.
This means that 5 out of 1,000 Norwegians at any time suffer from ulcerative colitis or Crohn’s disease. (Photo: istockphoto.com)
While it is true that there are not as many new cases of IBD each year compared to other diseases – perhaps 20 cases per 100,000 people – this number does not fully describe the clinical reality. These are chronic conditions, and although the health impact of the diseases varies from person to person, an individual will normally have a period of 10 to 20 years with active disease. This means that 5 out of 1,000 Norwegians at any time suffer from ulcerative colitis or Crohn’s disease.
We estimate that there are approximately 2.2 million patients in Europe with these diseases. They need medication, surgery and perhaps most often, regular contact with the national health service.
These diseases typically start at a young age, usually in individuals between 15 and 25 years old. One-quarter of all cases are diagnosed by paediatricians. IBD patients are thus affected during what is perhaps the most important part of their lives, when they should be studying, establishing their careers and raising a family.
There is no cure for ulcerative colitis or Crohn’s disease, but there are drugs and other treatments that aim to induce remission and to otherwise reduce the impact of IBD on daily life. Some of the drugs are easy to use and have minimal side effects, others require careful monitoring by experienced clinicians. The cost of drugs for an individual patient varies from about NOK 1000 to well over NOK 100,000 per year. Given all these factors, it is safe to conclude that chronic intestinal inflammation is a major problem for patients and costly for the national health service.
What causes ulcerative colitis and Crohn’s disease? The gut usually tolerates the presence of a wide variety of bacteria without any detrimental inflammation, but in patients with ulcerative colitis and Crohn’s disease, the gut has somehow lost this “tolerance”. This results in an inappropriate inflammatory response, and much of the research in the field is designed to understand why and how this takes place.
The IBD Research Group at NTNU and St. Olavs Hospital/the Central Norwegian Health Authority has been built up over the past few years. The principal investigators are clinical specialists in digestive diseases and also experienced laboratory scientists, and the group is now part of CEMIR and positioned to work in a close collaboration between clinical medicine and advanced molecular inflammation research.
The group has a large biobank of intestinal tissue samples, blood samples and relevant clinical information collected with consent from patients and healthy volunteers. This material has been used to form hypotheses about how the inflammation mechanism is activated in patients with established ulcerative colitis or Crohn’s disease.
Researchers in the project are primarily examining mucosal samples using advanced methods that allow them to detect the activation of all genes in a single tissue sample. The mucosa from patients with IBD contains several thousand activated genes that are potentially important in the inflammatory reaction. The most interesting findings are followed up by doing a microscopic examination of tissue samples, where we can determine the types of cells in which the genes are activated. We can then determine how to best proceed with specific, detailed laboratory studies.
We have already made several important findings from the analyses of these clinical tests, two of which are currently being intensively pursued. One is that we found a little-known group of proteins, the so-called REG proteins, to be strongly activated by intestinal inflammation.
The function of these proteins is almost unknown, but they likely play an important role, since they are upregulated as much as 80 times in the intestinal mucosa of IBD patients. It is conceivable that REG proteins are important in the inflammation and in the repair of damaged mucosa, and even that they have a direct effect on bacteria penetrating the mucus layer.
The second main finding from these studies is that a receptor which is part of the innate immune system, TLR3, appears to be important in the inflammatory process in IBD. TLR3 is found inside the mucosal cells and is stimulated by fragments of genetic material, particularly RNA. This discovery suggests that fragments of genetic material released by inflammation in the intestines can maintain the inflammation. It is also possible that RNA from viruses or other microorganisms in the gut may act via TLR3 to induce an inflammatory process.
All we can learn about the biological mechanisms of IBD, and especially results generated directly from the survey of patient material, is potentially important in working towards an effective treatment of ulcerative colitis and Crohn’s disease.
What do these findings mean for patients with IBD? Right now – nothing. But – the reason we don’t have a cure, or a treatment that controls inflammation in all patients, is that we still do not fully understand the disease process. All we can learn about the biological mechanisms of IBD, and especially results generated directly from the survey of patient material, is potentially important in working towards an effective treatment of ulcerative colitis and Crohn’s disease.
The official opening of the Norwegian University of Science and Technology’s four new centres of excellence (CoE) will take place on Monday 10 June. CEMIR, the Centre of Molecular Inflammation Research, is one of these new centres. CEMIR researchers will study new mechanisms that set off inflammatory responses. We hope this will provide us with information that could help in the development of new treatment methods and the diagnosis of diseases in which inflammation plays a crucial role. You can read more about CEMIR at http://www.ntnu.edu/cemir
In June there will be more blogs from CEMIR researchers.