Leibniz Lecture: Liver Diseases – A Global Health Challenge of the 21st Century
• German Research Foundation (DFG)
On May 10, 2016, the German Center for Research and Innovation (GCRI) New York and the German Research Foundation (DFG) hosted a Leibniz Lecture which focused on liver diseases, a 21st century global health challenge. Prof. Dr. Lars Zender, a gastroenterologist and oncologist from the University Hostpital Tübingen, received the Leibniz Prize, Germany’s most prestigious scientific research award, in 2014.
In his introduction, Prof. Zender explained that liver disease is an unmet medical need, despite presenting a major global health challenge. Liver-related disease is the only major cause of death that is still increasing. More than 1.5 million patients die of liver failure each year, with the number expected to double within the next 20 years. Zender spoke about the liver’s nearly unlimited capacity for regeneration due to active hepatocyte cells. He emphasized, however, that these cells only work in healthy livers. If the organ is inflamed, the regenerative capacity dramatically decreases.
The most common causes for liver disease, according to Zender, are hepatitis B and C, the fatty Western diet, and excessive alcohol consumption. Furthermore, 20 percent of the American population is affected by non-alcoholic fatty liver disease (NAFLD), which is indicated by fat bubbles in hepatocytes. He then explained how hepatocytes die due to diseases. As a result, scar tissue develops, a condition known as liver cirrhosis, which can lead to cancer.
Whereas hepatitis B is easy to cure, acute liver failure is currently untreatable. By decoding the molecular mechanisms of liver regeneration, researchers like Prof. Zender are able to work on new therapeutic methods. Prof. Zender’s team has shown that if MKK4 is inhibited, then the regeneration of hepatocytes is increased and can lead to a fully regenerated liver, as demonstrated in mice. One of the challenges Zender and his team face is the development of medication that can be used by human patients. Vast amounts of money are lost in the pre-clinical trial development of drugs. During his lecture, Zender mentioned that large pharmaceutical companies are starting to form new partnerships with academic researchers by creating academic drug discovery centers. His lab at the University Tübingen is one of three such centers in Germany.
One of the projects that is being executed in Zender’s Lab is to determine whether certain molecules can inhibit respective proteins. The goal is to find a molecule that can be applied to patients. Additional projects focus on cancer therapy, regenerative medicine, and cardiovascular disease. MKK4 plays a major role in these research projects, although certain challenges, for example, the large allosteric binding cavity, need to be solved before a drug can be administered to human patients on a larger scale.
At the conclusion of his lecture, Zender stressed the alarming increase of hepatocellular carcinoma (HCC). This is due to the large number of people living with chronic liver failure, which in most cases, leads to the development of HCC. The treatment options of liver cancer are very limited and currently only one method has been approved, despite its relative ineffectiveness. It only increases survival by 2.8 months until the tumors become resistant. However, as Zender demonstrated in his research, when combined with his new therapeutic method, the results are very promising. He illustrated this by discussing three patients who have been treated in his lab and so far have shown significant improvement in their condition. In the future, Zender hopes to develop his method further in order to find a working treatment option for acute liver failure and diseases.