IBD is the common abbreviation for inflammatory bowel disease, which is a group of disorders that cause inflammation in the intestine. The most common types of IBD are Crohn’s disease and ulcerative colitis.
These disorders are affecting more and more people. Today, around 40 000 people in Norway have been diagnosed with IBD. The incidence is increasing and is expected to grow to 58 000 people by 2030.
“IBD symptoms include bloody diarrhoea, weight loss, fatigue and abdominal pain. It is important to determine the right diagnosis early in order to start treatment,” says Ann Elisabet Østvik, a doctor specializing in IBD at St. Olavs Hospital in Trondheim.
Can take years to find the right medicine
“A lot of people have significant symptoms that affect their everyday lives long before they see their doctor for an examination, and some become so ill that they have to be admitted for intensive treatment or in the worst case, undergo bowel surgery,” the doctor says.
Elisabet Østvik performs a colonoscopy on a patient with IBD. During a colonoscopy, small pieces of the patient’s intestinal mucosa (biopsies) are removed and sent to the Gastroenterology Centre for research at St. Olavs Hospital. There, the biopsies are cultured into organoids. All patients included in the study have consented to the research. Photo: Janne Amalie Svit
IBD is a lifelong disease. Most patients are diagnosed as adolescents or young adults. Access to more medications has improved in recent years, but the drugs that work on different patients vary greatly. And in IBD patients, there are no biomarkers that can indicate the likelihood that a drug will work.
“Many patients spend several months, and sometimes years, trying and failing before they find the right type of treatment. This greatly impacts IBD patients’ quality of life,” says Østvik.
Testing in large numbers – all at the same time
A research team is now studying how to find the right medicine by taking tissue samples from patients’ intestinal mucosa. Organoids, often called “mini-intestines,” are created from these tissue samples, which are then used in drug trials.
Central to the work is a very special laboratory at SINTEF.
“Many scientists use organoids in IBD research, but what’s unique here is that we can compare what we find in our experiments in the lab with what patients actually experience.”
“In the laboratory, we have a fleet of robots that can collect several patient samples in the same experiment. This way, we can test a lot of samples against a list of drugs that can have different effects. It would be extremely time-consuming to do this task manually,” says Tonje Husby Haukaas, a SINTEF researcher who is working on automating the studies.
–It would be extremely time-consuming to do this manually, says SINTEF researcher Tonje Husby Haukaas. Photo: Silje Grytli Tveten
More precise treatment for each patient
The goal is a study with colonoscopy where tissue samples are harvested for organoids. These would then be grown and tested by robots.
What are organoids?
Organoids are small, three-dimensional structures ("mini-organs") that researchers create in the laboratory using stem cells taken from patients. One of their properties is organizing themselves so that they mimic the structure of the organ, but the organoids are much smaller and simpler. Organoids retain the patient's genetic information and can mimic important functions from the organs they represent. They are often used in research to study diseases and test drugs.
“The tests can tell us which drugs are most likely to be effective for individual patients. This will allow us to tailor a more precise treatment for each patient,” says Haukaas.
The method can also help develop precision medicine for IBD patients.
“The tissue samples are frozen. This means that you just have to thaw them when you want to carry out tests. The system functions so that everything is in place to run tests with different drugs,” says Haukaas.
This robot makes it possible to test thousands of samples from the patient – all at the same time. This enables patients to receive medication more quickly at the individual level. Photo: Silje Grytli Tveten
Strong collaboration yields results
The work is being done at the InTRaCC – Gemini Centre – NTNU research centre. The Norwegian University of Science and Technology (NTNU), SINTEF and St. Olavs Hospital in Trondheim, as well as the University of Oslo, collaborate on their IBD research.
The researchers have been building up the biobanks for a long time. Patients have been followed up from the time they were diagnosed. Now researchers have also put good methods for investigating the effects of medications in place, but this is the first time that they have been tested on a large scale with patients.
The results are encouraging.
“We’ve seen what medication effects we can detect in laboratory-grown organoids, and can observe when they align well with the effects we can see in the patient,” says Torunn Bruland, head of the organoid lab at NTNU.
The image shows the similarity between a gland in the intestinal mucosa of a patient and the mini-intestines that are grown in the laboratory. The cells are labelled with different immunofluorescence dyes. Photo: NTNU
“Many scientists use organoids in IBD research, but what’s unique here is that we can compare what we find in our experiments in the lab with what patients actually experience,” Bruland adds.
Worst for children and young people
Medical specialist Ann Elisabet Østvik emphasizes how important it is to establish faster methods for finding the right medicine.
“All the symptoms that patients experience lead to a decreased general condition and quality of life. Many are unable to go to work or school. They are also affected in crucial years of their life when they need to pursue their education and start working,” she says.
Children are particularly vulnerable as these diseases can cause stunted growth and delayed puberty. Some of the symptoms are taboo or embarrassing, which also tends to affect young people the most.
The doctor stresses that finding an effective treatment for children and adolescents is especially urgent.
Facts about the research collaboration:
The Gemini Centre InTRaCC – Individualized Treatment and Research on Crohn’s and Colitis – is a strategic collaboration between research groups at NTNU and St. Olavs Hospital, the University of Oslo/Ullevål University Hospital and SINTEF. Together, the partners combine their expertise and resources to carry out major research projects that can help develop more precise and personalized treatment for patients with inflammatory bowel disease (IBD).
These are the three partners:
CAG IBD – Precision Medicine in Inflammatory Bowel Disease is a clinical academic group (CAG) that aims to bring together research on inflammatory bowel disease and the development of clinical skills across universities, hospitals, clinical departments and groups of healthcare professionals in Central Norway.
The IBD research group at the University of Oslo/Ullevål University Hospital has established large IBD registries and biobanks (IBSEN). They focus primarily on epidemiological and clinical treatment studies to understand disease patterns and develop better and more personalized prevention and treatment.
SINTEF Biotechnology and Nanomedicine's Screening Laboratory has one of Norway's best-equipped laboratories for laboratory automation and screening of biological samples. The work here is particularly focused on automated cultivation of patient-derived organoids.
