Precision medicine for the liver
As part of the StopPSC project, a team from Hannover Medical School (MHH) and the Helmholtz Centre for Infection Research (HZI) is researching new therapies for chronically inflamed bile ducts.
Approximately one in 10,000 people in Germany is affected by primary sclerosing cholangitis (PSC). In order to digest fats from food, the intestine needs bile. This is produced in the liver and from there it reaches the intestine via the gallbladder and bile ducts. If these bile ducts become chronically inflamed, this can lead to agonizing itching, fatigue and weight loss as well as liver failure. PSC often results in a liver transplant. The disease usually develops between the ages of 30 and 50.
There is currently no cure for PSC. It is only possible to treat the symptoms. For example, antibiotics are used, but these have too broad an effect and lead to resistance. As part of the ongoing "StopPSC" project at the German Center for Infection Research (DZIF), a team of scientists from MHH and HZI is now researching a new therapeutic approach based on flu drugs.
"We are developing tailored therapies for primary sclerosing cholangitis (PSC) using optimized active substances to improve the prognosis of patients," says the project's spokesperson, Prof. Dr. Benjamin Heidrich. He works at the MHH's Department of Gastroenterology, Hepatology, Infectiology, and Endocrinology and is also deputy coordinator of the DZIF research area Community-Acquired Infections at Mucosal Interfaces.
Research team develops pathoblocker
The basis for the research is that a complex community of different types of bacteria lives in the bile ducts—even in healthy people. If certain types of bacteria become more prevalent, the disease worsens. This is not about the bacteria themselves, but about the enzymes they produce: the so-called sialidases attack the cells of the bile ducts so that they are no longer protected from the bile acid and become inflamed. In the StopPSC project, the researchers now want to develop an active substance that can specifically inhibit the sialidases. Such active substances that inhibit the pathogenic substances produced by the bacteria are called pathoblockers.
The team first investigates on the computer and then in the laboratory whether certain flu drugs work strongly and precisely enough. They then want to find out how the active substances get into the bile ducts and how they can be distributed well there. Their aim is to develop a patent that companies can bring to clinical application. StopPSC builds on previous research within the Cluster of Excellence RESIST and the DZIF.
The state of Lower Saxony and the Volkswagen Foundation are providing financial support for the project "Sialidase targeting pathoblocker therapy for primary sclerosing cholangitis" (StopPSC): two million euros are being contributed as part of the "zukunft.niedersachsen" program. The program funds projects that aim to develop new diagnoses and therapies for rare diseases. Diseases are considered rare if they affect fewer than five in 10,000 people. Rare diseases are often particularly difficult to diagnose and treat.
Source: MHH press release
