At MetaboKin, we believe that metabolism is a key to understand many of our modern lifestyle diseases. However, in today’s pharmaceutical and clinical practice, metabolic changes are not sufficiently considered. A basic obstacle is a difficulty to assess metabolic alterations experimentally or clinically. Luckily, decades of biochemical research have put us in a spot, where we can simulate the functionality of a metabolic network based on the properties of its molecular constituents. We are convinced that including metabolism throughout the different phases of drug development will increase the chances of clinical success. In the clinic, the personalized assessment of metabolic changes in different organs will enable better diagnostics and improve the evaluation of treatment options and therapy planning for many modern diseases.
Our mission at MetaboKin is to bring metabolism into drug development and clinical routine. MetaboKin improves the drug development process by providing a better understanding of the underlying metabolic changes, which are the basis for many modern diseases associated with adipositas and metabolic syndrome. We develop virtual cells for different organs that can assess metabolism based on the kinetic properties of hundreds of metabolic enzymes. With these virtual cells, one can simulate metabolism instead of measuring it. They provide an in-depth characterization of organ metabolism that cannot be achieved otherwise. We go deeper in the field of metabolism than conventional discovery processes because we address the underlying molecular changes. Our virtual cells are a valuable tool for drug development research purposes but also for clinical decision support. In drug development, they enable a more precise target identification, the evaluation of different modes of action, the simulation of the effects of drugs, and a better stratification of patients for clinical trials. In the clinic, personalization of our virtual cells allows individual assessment of organ metabolism intending to support diagnoses and improve therapy recommendations.
About the project
Our virtual cells are not disease-specific: MetaboKin can be used to evaluate metabolism under various physiological and pathological conditions, like different dietary regimes, rest and stress conditions, or specific medications. The virtual cells can be personalized by patient-specific proteomics data, obtained for example by biopsies, and customizable to various research questions. We are in the process of developing virtual cells for other organs, e.g. kidney, fat tissue, lung, and muscle tissue.
In the liver, metabolic syndrome manifests as non-alcoholic fatty liver disease (NAFLD). It affects more than 25% of the world's population. Untreated NAFLD develops into more severe disorders like non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and liver cancer (HCC). Despite pharmaceutical companies’ significant efforts in recent decades, there is still no available drug treatment for NASH. It is critical to improve our understanding of the underlying metabolic changes and to develop new treatment options for NASH; however, it is rather difficult to pursue this, both experimentally and clinically. Our virtual liver cell can help to unravel metabolic changes occurring in the liver during NAFLD, NASH, diabetes, and cancer.
The brain is metabolically one of the most expensive organs accounting for around 20% of the body’s oxygen consumption while making up less than 2% of the body weight. In contrast to other organs, energy reserves in the brain are scarce. Therefore, the brain has to rely on a continuous supply of nutrients and oxygen making it extremely susceptible to energy-demand supply mismatch. Experimental information about short-term dynamics of energy metabolism in neuronal tissue is low because metabolic adaptations to varying energetic needs occur within seconds making them invisible to classic experimental techniques. Our virtual cells allow simulating metabolic changes in neuronal tissue. This allows us to investigate neuronal energy-supply demand relations at very different conditions like varying activity states, during hypoxia, or under the influence of anesthetics. It can be used to assess metabolic changes occurring in pathological conditions like epileptic seizures, neurodegenerative diseases, or brain cancer.
Heart failure is a growing public health concern. Although alterations in cardiac metabolism are understood to be an underlying component in almost all cardiac myopathies, the potential contribution of myocardial metabolism to the reduction of cardiac performance is not well understood due to the lack of non-invasive methods allowing an in-depth characterization of cardiac metabolism. Our virtual cells may help to fill this gap. In combination with proteomics data, they allow disease-specific and individualized computer simulations of the cardiac energy, carbohydrate, lipid and amino acid metabolism at varying workloads and different physiological conditions (e.g. overnutrition or diabetes). In particular, our computational approach may reveal the energetic reserve capacity of the heart and may contribute to metabolic characterization and risk assessment.
What we are looking for
We are looking for partners within pharmaceutical companies to test our virtual cells in pilot projects. We are also looking for cooperation with proteomics facilities to test our solution on a broad spectrum of proteomics data. Finally, we are looking for cooperation with physicians to test clinical applications.
Partner to assess metabolism
in your research questions and
make most out of your proteomics data!
Currently, MetaboKin offers virtual cells for the brain, liver, and heart incorporating hundreds of organ-specific metabolic enzymes. Taking into account the regulation of each enzyme by substrate availability, allosteric regulation, and interconversion through hormonal signaling, they enable simulation of the complex relationship between nutrient supply, protein abundance, and metabolic demand.
Prof. Hermann-Georg Holzhütter
(Institute of Biochemistry)
Dr. Christion Hudert
(Department of Pediatric Gastroenterology, Nephrology
and Metabolic Medicine)
Dr. Augustin Liotta
(Department of Anesthesiology and Intensive Care)
Prof. Titus Kühne
(Institute of Computer-assisted Cardiovascular Medicine, Charité; and Deutsches Herzzentrum Berlin)