Evaluating cirrhosis 'live' and accurately at the cellular level

21 December 2011

Detlef Schuppan and his colleagues are developing a revolutionary method that will make it possible to evaluate the progress of fibrosis and cirrhosis at the cellular level and to even view the effects. For this work, the physician and chemist has been awarded the most highly endowed research grant of the European Union, the ERC Advanced Grant.

His office is not overly grand. Just recently his book shelf toppled over and now his reference books are stacked along the wall. "A temporary solution," Professor Detlef Schuppan (57) tersely remarks. He has just finished an endoscopy examination and his next appointment is fast approaching. "It's all about procuring third-party funding," he says. In the meantime, he is at leisure to talk about his research and his groundbreaking methods, the development of which led to his being awarded the Advanced Grant of the European Research Council (ERC) in 2011. "It amounts to EUR 2.5 million over a period of five years - enough to achieve something." Not surprising, in view of the fact that this is the most highly endowed research grant in the European Union.

Rapid conversion of theory into practice

Schuppan came to work at the 1st Department of Medicine at the University Medical Center of Johannes Gutenberg University Mainz (JGU) in December 2010. Fibrosis and celiac disease are the research focus of Schuppan, who holds a professorship in molecular and translational medicine. "Perhaps it would be best to explain the term 'translational' first," Schuppan says. "The idea is to find practical applications for the results of fundamental research as quickly as possible." This is particularly important in the medical field. "This is to the benefit of the patients and all other parties involved."

These parties also include pharmaceutical companies. "They keep on coming up with interesting active substances, but pre-commercial development is an enormously expensive exercise." This is particularly the case when it comes to conditions such as organ fibrosis in which the efficacy of the administered substance is difficult to assess. The most widely known form of this disorder is liver fibrosis, the advanced stage of which is called cirrhosis. Physicians estimate there are at least 250 new cases a year for every 100,000 of the population. In the presence of this disease, nodules develop in the liver and scar tissue forms where there should be none. Other organs such as the lungs, kidneys and skin may also be affected by fibrosis.

Diagnosis of fibrosis and cirrhosis

The progression of fibrosis and cirrhosis can be difficult to diagnose. For the purposes of testing new drugs, it is the case that hundreds of patients are required even during the initial phase of the related clinical trials. It can take years until it becomes clear whether and how a substance is effective in a given patient group. "Unfortunately, this approach is associated with a high risk to patients," Schuppan points out.

However, it is also possible to take samples of liver tissue. "But we can only take very small samples and this makes for potentially large statistical sampling errors, so that we again need to have large collectives of subjects from whom we can obtain samples."

Reducing the costs by a factor of 100,000

Schuppan and his colleagues are now working on a method that is likely to be revolutionary in this field. "We will be reducing the outlay by about a factor of 100,000. Where previously 500 or 1,000 patients were treated over a period of many years, we now only need five patients for three or four days."

Professor Schuppan makes use of tiny amounts of radioactively labeled substances. "They adhere to small molecules on the surface of specific cells." It is these cells that are involved in the formation of the undesirable scar tissue. This makes it possible to evaluate fibrosis and cirrhosis in real time and more or less at the level of individual molecules. What was once difficult to diagnose can now be accurately observed so that when a doctor administers an active substance, researchers can then immediately see how it works. "This is not only true for the liver, but also for the lung or the pancreas. The same principle applies in each case."

Unique research

The research carried out by Schuppan and his colleagues is a worldwide unique. "If things go well, we will be able to test the first substances on small groups of patients in two to three years' time," he says. This is only the beginning, however. "We are interested in therapies that reverse cirrhosis and break down the scar tissue."

Quite apart from this, there are many areas in which it would be a great help to be able to assess individual body cells and thus intervene at cellular level as well. "You can improve efficacy and reduce the risk of side effects if you are able to expose only the cell you wish to treat to the active substance."

This research program will now be financed by the Advanced Grant for the next five years. Schuppan pauses for a moment. "And this is just one among our many current projects," he goes on to say. Progress is also being made on celiac disease, a condition that makes people intolerant of gluten. But that's all for now, as his next appointment is already waiting to consult him in his small office. "There's lots more I can tell you," promises Schuppan, as he says good-bye.