09 April 2014 - PROFILE STEPHAN URBAN
First Professor of Translational Virology
It all began 20 years ago with Pekin duck breeding in Kirchheim near Heidelberg. At the time, duck was the model of choice for hepatitis B research, which Stephan Urban also used to discover a peptide that could inhibit the duck hepatitis B virus from entering the liver cell. Today, an analogous peptide called Myrcludex B, a promising virus blocker, is undergoing clinical trials for both healthy test persons and people with chronic hepatitis B infections. Stephan Urban is following the first trial results with anticipation. He has been holding the first DZIF professorship for “Translational Virology” in Heidelberg since 1 April.
Although a vaccine against hepatitis B (HBV) has been available since the 1980s, the viral infection still causes a global health problem. HBV is one of the most common viral infections. Two billion people have had contact with the virus, and approximately 350 million people worldwide are suffering from chronic HBV infection which can lead to cirrhosis and cancer of the liver. The drugs currently available delay the development of potential complications, but only cure the disease in a small number of cases. “I therefore think that developing novel and more effective drugs is a very important task,” Urban stresses. “Accomplishing higher cure rates would be an enormous success.” The new peptide, Myrcludex B, which the virologist discovered almost 20 years ago, could contribute to this. “At the time only very few researchers would have thought that a peptide could successfully end up in hospitals,” he remembers with a grin. “Too expensive, too unstable, too inefficient…” But Myrcludex B proved to be extraordinarily stable. Additionally, it very specifically targets the liver and extremely small doses can block the hepatitis B virus from entering the liver cells.
The mechanism of action, deciphered by Stephan Urban and his research team, is easily explained. The peptide is a protein fragment from the virus envelope and binds specifically to liver cell sites where it inhibits molecular docking of the dreaded virus. It fits exactly into these sites, like a key into a lock, and remains there blocking the site for the active virus. Urban explains the latest research results: “We know today that the receptor to which the virus binds is a bile salt transporter. The virus misuses these transporters as an entry channel. We need to further investigate whether molecular docking to bile salt transporters causes adverse reactions in patients. For this drug candidate, we may perhaps even discover a whole new therapeutic area which has nothing to do with hepatitis B.”
Currently, curing chronically ill patients has the highest priority. Urban is convinced, “Combination therapies with approved drugs like interferon and nucleoside analogues such as tenofovir and entecavir are conceivable, but there are also many other possibilities.” He enthusiastically envisages: Mother to child transmissions being prevented very effectively, re-infection rates after liver transplants being stopped, and at much lower costs than previously … possibly, the peptide not only blocks the entrance of new viruses but may also induce immune responses against them. The antibodies would then inhibit the infection of new cells on a long term basis.
When Stephan Urban speaks about his work, it quickly becomes evident that it is no accident that he is doing research. Even as a school student he always wanted to get to the bottom of things. He started doing experiments in the cellar of his parents’ home in in Neustadt / Weinstraße, and to this day is glad that his parents were not always aware of what he got up to. He won the national youth science competition “Jugend forscht”, which encouraged him to begin his studies in chemistry and biochemistry, and completed his degree at the University of Tübingen in 1991. He had actually planned a stay abroad for the time after his PhD thesis in 1995 at the Max Planck Institute in Martinsried near Munich, but it all turned out differently: He found love in Germany and was offered an attractive position at the Center for Molecular Biology of the University of Heidelberg with Professor Heinz Schaller which finally convinced him to stay in the country, in Palatinate that is.
And he has not regretted it. “Looking into the vineyards still warms my heart,” the scientist admits. “I love the area and enjoy cooking, and occasionally go on outings to nearby Alsace where I can buy all the right ingredients.” But recently, he has not managed to do this all that often, because his research projects have been running at a high intensity. Since 2002, the lead substance Myrcludex B has been optimised, the toxicity studies have been completed, and in 2011 the Federal Institute for Drugs and Medical Devices BfArM approved testing the candidate drug on healthy subjects for the first time. Urban has many reasons to vividly remember the week in which the first human being was treated with Myrcludex B in Heidelberg: The first day of treatment took place a day after his 50th birthday, and his son, Viktor, was also born. “A very special week,” he remembers with shining eyes.
At the DZIF, Urban sees a great opportunity to develop his peptide further in collaboration with the biotech company MYR-GmbH which has been involved since early on. “I come from the field of basic research and still find this extremely important. Myrcludex B is a very good example: We never planned to develop a drug from the originally funded basic research projects. This emerged on its own at a certain point in research. Pure research is also always a productive source for applications. One need only recognise this and obtain appropriate funding.” The BMBF and the DZIF do very good work in this respect, as he already knows. Discovering an active agent and characterising it in the laboratory in one thing. Developing it into a drug and possibly bringing it onto the market is quite another. The DZIF has always focused on this goal.
The goal is in sight for Myrcludex B. Urban and his team are anxiously awaiting the results of the first phase II trials which are being conducted in Russia, funded by the licensee and DZIF contract partner MYR-GmbH. They are being conducted parallel to the DZIF-funded phase I trial in Heidelberg in which 60 patients have already been included. Stephan Urban will still be involved in research on Myrcludex B and its therapeutic possibilities for a longer time. He is optimistic and explains, “There is a lot of rethinking currently going on in the field of HBV: Which new active agents can we combine to develop curative treatment?” His future continues to look active: In his personal life his son will be keeping him on his toes, and for work he will be commuting from Neustadt to Heidelberg daily when he is not attending conferences. “I enjoy travelling by train because that is where I can work best.” He saves his Karmann-Ghia convertible for his outings to the Alsace, for which he will hopefully still manage to spare some time despite all his successes.