Published on May 4, 2021
Roman-Ulrich Müller, M.D., University of Cologne
How did you first get involved in PKD research?
Roman: In 2004, I spent a part of my scientific training at Rockefeller University (NYC) in the laboratory of Thomas Tuschl. Thomas is an outstanding scientist who pioneered the field of so-called small regulatory RNAs. These small RNAs are molecules that have an enormous impact on gene expression and have a huge therapeutic potential.
Back then, I found that one of these RNAs (a member of the microRNA-17-92 family) was a regulator of PKD1 (later published in the Journal of Molecular Medicine, 2013), the gene most commonly affected in ADPKD. Together, with the clinical importance of PKD which I learned about in medical school at the University of Freiburg (Germany), this finding raised my interest in PKD research.
This interest was also the reason why we started to set up a large prospective cohort study at the University of Cologne (AD(H)PKD) to enable clinical research in PKD. More than 800 patients have now contributed to this initiative. We’re very grateful for this opportunity to lay the foundation for further advances in the PKD field.
What are you working on currently?
Roman: On the one hand, we’re continuing our work on the molecular mechanisms of cyst formation in PKD in the laboratory. On the other hand, and most importantly, we’ve started translating basic research results from the bench to the clinical trial setting with a focus on dietary interventions. This initiative is based upon findings by the group of Thomas Weimbs in Santa Barbara, with whom we closely collaborate on this topic. He found that simple diets which mimic fasting profoundly inhibit the growth of kidney cysts in animals with PKD. These diets induce the state of “ketosis” that allows fat reserves to be used for energy instead of blood sugar.
Based on these findings, we’re currently running two clinical trials that examine ketogenic dietary interventions in ADPKD—RESET-PKD (NCT04472624) and KETO-ADPKD (NCT04680780). KETO-ADPKD was enabled by a grant from the PKD Foundation and tests two well-established diets that induce ketosis: (1) fasting and (2) a high-fat/low carb ketogenic diet. ADPKD patients will be treated with either diet for three months to find out how well they tolerate these diets, how safe they are, and if they have an impact on kidney volume.
The results will be crucial for the design of a subsequent trial to test whether one of these diets slows disease progression in the long term in a much larger number of ADPKD patients.
What would you like the patient community to know about your research?
Roman: PKD is a disease that comes with a considerable burden for most of the affected patients. For many decades, treatment of PKD was limited to supportive measures. However, the last decade has changed the situation regarding PKD research and emerging therapies a lot. With tolvaptan, the first targeted treatment for ADPKD became available. Tolvaptan doesn’t cure the disease, it only slows down kidney function over time. Consequently, additional therapeutic strategies are an important aim. Fortunately, there are a number of different candidate drugs that are actively studied in clinical trials and we’ll learn more about their effect over the next years.
Importantly, however, we’re only just learning that treatment of PKD is probably not limited to pharmaceutical strategies. It’s clear that a healthy lifestyle (e.g., maintenance of normal body weight) plays an important role as well and nutrition (e.g., ketogenic diets) may actually be a powerful tool to ameliorate disease progression. It’ll now be of utmost importance to study such approaches in clinical trials in order to confirm efficacy and safety in humans.
Do you have a personal connection to PKD?
Roman: None of my family members or close friends are affected by PKD. However, if you take care of a large number of PKD patients as their medical doctor, the connection to this field, to the challenges the disease poses to affected persons, and the feeling of a need for therapeutic options, do indeed get quite personal.
What excites you most about this research?
Roman: Translational research is absolutely fascinating to me. Linking cellular biology with metabolic changes and designing tools for how to target these changes for the treatment of human disease in one research pipeline, and in collaboration with outstanding colleagues, is a wonderful task.
What are some of your personal interests outside of research?
Roman: I love learning new things, both in and outside of work. Outside of research, traveling to see new places in the world and getting to know people and their cultures is one of my favorites. Let’s hope we’ll all get through the current difficult situation with COVID-19 soon to make interactions (both scientific and personal) around the world possible again.
Anything else you’d like to share?
Roman: I’m deeply convinced that the close interaction between patients, doctors, scientists, and patient advocacy groups is an important piece in the puzzle toward improved PKD management in the future.
The PKD Foundation is the largest private funder of PKD research in the U.S. Since 1982, we’ve invested over $50 million in more than 1,300 research, clinical and scientific grants, fellowships, and scientific meetings. Each year, the Foundation identifies and supports the work of scientists and researchers from around the world who look for ways to treat and eventually cure PKD. Our vision is to #endPKD. Donations fund necessary research that leads to more effective treatments and ultimately a cure for PKD.