University Medical Centre Groningen (UMCG)
In search of the origins of rare bile duct disease
Primary Sclerosing Cholangitis (PSC) is a rare disease in which bile ducts become inflamed both inside and outside the liver. Narrowing arteries form due to scarring, which in turn lead to harmful blockages of the bile in the liver. The cause is unknown. However, the earlier the condition is identified, the better the treatment possibilities. UMCG is conducting research in this field.
PSC is a chronic, progressive disease of the liver and bile ducts. It’s a rare but serious condition that initially occurs in latent form and is diagnosed on average around the age of 38. Arno Bourgonje, postdoctoral physician-researcher, encountered PSC while researching inflammatory bowel diseases (IBD) with professor Rinse Weersma. These include chronic inflammatory diseases such as ulcerative colitis and Crohn’s disease. ‘People with PSC often also suffer from such illnesses. The cause of PSC is unknown, but it’s very likely to be an auto-immune disease. And potentially the microbiome of the intestines – the community of naturally occurring bacteria, viruses and yeasts – plays a role in its occurrence.’
Early detection
PSC is a progressive disease and there is no cure yet. Patients rely on treatment for its effects. About half of patients eventually need a liver transplant. Bourgonje: ‘Currently, PSC is often only detected late, for example when patients with IBD have impaired liver tests. In that case, the scarred bile ducts are no longer treatable. It might be possible to prevent these problems by suppressing the inflammatory response in the bile ducts. But this early stage doesn’t present any symptoms and we are unable to detect it.’
Venture Capital
Important initiatives struggle to take off when government and companies are reluctant about investing. This might be due to the associated risks or the absence of financial gains. Dioraphte provides funding for essential initiatives in need of a boost, like research into rare diseases. Are the results promising? If so, government and pharmaceutical manufacturers are more likely to join in for the next phase.
Antibody detection
In patients from the two PSC centres of expertise (see this article below), physician-researcher Fokkelien Veenstra will be exploring ways to detect the disease at an early stage for her PhD. For this, she will apply an innovative laboratory technique previously used by Bourgonje in studies on IBD. Veenstra: ‘It seems that PSC occurs in part due to an abnormal activation of the patient’s immune system. As a result, it turns against proteins in the patient’s own body. In the laboratory, we intend on mapping out a patient’s antibody repertoire. Without this new lab technique – which is very costly – it is impossible to do something like this accurately. The idea is to discover antibodies specific to PSC. If we find those, we will have quantifiable indicators- biomarkers – that may allow us to detect the disease earlier.’
Better prognosis
Bio-markers are not only relevant for an early diagnosis, Bourgonje continues. ‘If you have an overview of a specific patient’s immune reaction, one can also attempt to predict the progression of their disease. For example, this allows us to gain an insight into high-risk groups who show a higher chance of a more severe PSC outcome. And if we learn more about the onset of the disease, we can consider options for early treatment that will prevent complications.’
Reliance on follow-up grants
Both researchers know how difficult it is to find funding for rare disease research. Bourgonje: ‘You usually get funding more easily if a study can lead to a clinical application sooner. But we are not that far yet in PSC. We are in the phase of trying to understand which biological mechanisms cause the disease. That requires time-consuming fundamental research. It is precisely such research that Dioraphte is brave enough to fund, in the belief that we can then tap into other sources of funding. If we indeed manage to find those biomarkers, then a diagnostic or predictive test will come into play. I have high hopes that other funding bodies will then follow suit.’
There are two PSC centres of expertise in the Netherlands. The centre in Groningen is led by professor Rinse Weersma, the one in Amsterdam by professor Cyriel Ponsioen.