Fighting Heart and Kidney Diseases
Searching for a needle in a haystack: Dr. Peter Kolkhof’s research team identified a drug candidate to treat kidney diseases.
I was always curious about biology and medicine. Questions like “What is the basis for diseases?” and “How can we improve patient’s lives?” have fascinated me since I was in school. I´m lucky. Working at Bayer, I’m often finding answers to these questions. I search for novel drug candidates that can help fight life-threatening diseases.
Living for Research
Discovery and developing new drugs are long-term processes: For almost 17 years, I’ve been working on an agent to treat chronic heart and kidney diseases. In 2000, I launched a research project to identify a novel small molecule inhibitor for a receptor protein that has a crucial role in the development of cardiovascular and renal diseases. The multidisciplinary team I lead between 2004 and 2008 continuously optimized initial high throughput-screening hits, and later more advanced drug candidates. This research finally led to a promising drug candidate which inhibits mineralocorticoid receptors.
In a phase II trial with just over one thousand heart-failure patients, this drug candidate demonstrated an improved outcome regarding mortality and hospitalization. In another phase II trial, which assessed albumin levels in the urine of 823 patients with diabetic kidney disease, this drug candidate also dose-dependently showed a reduction in kidney damage. These are very promising results against such severe illnesses. Renal damages can be due to overactive mineralocorticoid receptors affected by aldosterone, a natural hormone. This receptor over-activity can lead to inflammatory and fibrotic processes that damage the heart and kidneys. Our active ingredient aims at preventing this process by blocking aldosterone’s binding to its receptor.
Passion, Patience, Luck - and 11,000 Patients
Bayer is currently investigating the mentioned promising drug candidate in two large phase III trials, aiming to recruit 11,000 patients in more than 40 countries worldwide. The whole team considers this as a marvelous achievement. The greatest satisfaction for a preclinical pharmacologist like me is to be a member of the research and development team right from the beginning. Passion and patience are ‘must-have’ skills of every drug discovery team, but you also need some luck to discover a substance that can make it through the clinical phases. Sadly, such discoveries rarely happen, only about one percent of the early candidates ever make it this far, and the luck factor is hard to accept for some researchers.
From Wuppertal to Wuppertal
I’ve been working on biology almost all of my life. I still work with the topics from my high school final exam: gene regulation and transcription factors. But now I’m working on them in a laboratory. I studied biology at Cologne University, with pharmacology, biochemistry and molecular biology as major subjects. One day, a former head of Bayer research gave a university lecture about the tremendous opportunities in applied science. After my graduation in 1994, I came back to Wuppertal to work at Bayer’s Institute for Cardiovascular Research.
I grew up about 500 meters away from the research center I work at right now. I left the area for an assignment at our former research department in Milan, Italy, from 1999 to 2001; then I returned. My family still lives in the Wuppertal area today. During my leisure time, I like to hike in this region. Even from my office, I love the view of green hills and meadows.
CV Peter Kolkhof
| 1965 | Born in Wuppertal |
| 1990 | Master’s degree from Cologne University (Germany) |
| 1994 | Doctorate |
| 1995 | Post Doc at Bayer |
| 1996 | Lab Leader at Bayer |
| 1999-2001 | Department Head at Bayer in Milan, Italy |
| 2002-today | Leader of several preclinical projects at Bayer in Wuppertal |
| 2004-2008 | Preclinical Project Leader, Finerenone |
| 2010-today | Principal Scientist Cardiovascular Research |
Selected Publications
Mineralocorticoid receptor antagonists: 60 years of research and development
Kolkhof P, Bärfacker L
J Endocrinol. 2017;234, in press (July 2017)
Steroidal and Novel Non-steroidal Mineralocorticoid Receptor Antagonists in Heart Failure and Cardiorenal Diseases: Comparison at Bench and Bedside.
Kolkhof P, Jaisser F, Kim SY, Filippatos G, Nowack C, Pitt B.
Handb Exp Pharmacol. 2016 Nov 10. [Epub ahead of print]
Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial.
Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, Remuzzi G, Rossing P, Schmieder RE, Nowack C, Kolkhof P, Joseph A, Pieper A, Kimmeskamp-Kirschbaum N, Ruilope LM; Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy (ARTS-DN) Study Group.
JAMA 2015;314:884-94.
Nonsteroidal antagonists of the mineralocorticoid receptor.
Kolkhof P, Nowack C, Eitner F.
Curr Opin Nephrol Hypertens. 2015;24:417-24.
Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury.
Kolkhof P, Delbeck M, Kretschmer A, Steinke W, Hartmann E, Bärfacker L, Eitner F, Albrecht-Küpper B, Schäfer S.
J Cardiovasc Pharmacol. 2014;64:69-78.
Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics.
Kolkhof P, Borden SA.
Mol Cell Endocrinol. 2012;350:310-7.
Selected Patents
Co-inventor of approximately 50 patent applications.
Awards
2008 und 2009: Global Drug Discovery Award; Drug Discovery Organization, Bayer
2012: ESC Award fort he winning moderated poster presentation given at the Annual Meeting of the European Society of Cardiology
2014: Otto Bayer Medal; Research Award Bayer AG