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Scientists at the BIH recently discovered that an infection with the new coronavirus SARS-CoV-2 is often severe when the immune system reacts with an augmented immune response. During this research they came across an interesting target molecule on immune cells. Researchers at Bayer had already developed a substance against precisely this target molecule several years ago and tested it extensively in studies. The therapeutic substance proved to be well tolerated, but not effective enough for the intended indication. It will now get a second chance as a COVID-19 drug.
The German Federal Ministry of Education and Research (BMBF) is funding the cooperation between the Berlin Institute of Health (BIH) at Charité, the pharmaceutical company Bayer and three other hospitals (Leipzig and Würzburg university medical centers and the Unfallkrankenhaus Berlin) on the clinical testing of a COVID-19 drug to the tune of around €3.5 million.
Vaccination and mass testing are the most important tools in tackling the COVID-19 pandemic. In addition, safe and effective drugs are needed to treat those who become sick. It is against this backdrop that the BMBF is funding research into drugs against COVID-19. “Unfortunately we have to expect that people will continue to fall ill with COVID-19 in the foreseeable future. We therefore urgently need to increase our arsenal of effective drugs,” said Federal Research Minister Anja Karliczek when announcing the eight funded projects aimed at developing such drugs.
Augmented immune response wreaks havoc
One of these projects is based on research conducted at the BIH. Professor Roland Eils, founding director of the Digital Health Center at the Berlin Institute of Health (BIH), and Irina Lehmann, BIH Professor for Environmental Epigenetics and Lung Research, together with colleagues from Charité - Universitätsmedizin Berlin and University of Leipzig Medical Center, discovered that the immune system plays a crucial role in severe progression of COVID-19. “Using single cell analyses, we found out that epithelial cells infected by the virus send a ‘distress call’ to the immune system,” says Eils. “However, the immune cells that migrate in response to viral infection occasionally overshoot the target and, with their exaggerated reaction, sometimes do more damage than the virus itself. So it was clear to us that any therapy would have to address the immune system’s role.”
Signaling molecules of the immune system, known as chemokines, are involved in the migration of immune cells into the airways. Epithelial cells and activated immune cells release chemokines and thus attract further immune cells. The immune cells have chemokine receptors on their surface with which they can “receive” the calls for help. “In our studies with single cell analyses we saw that one of these receptors in particular – chemokine receptor 1 (CCR1) – was associated with an augmented immune response and severe COVID-19 disease progression,” reports Lehmann. “So we had the idea to block this receptor in order to dampen the immune response.”
Bayer drug gets a second chance
The scientists led by Eils and Lehmann therefore starting searching for known blockers of this receptor – and actually found one at Bayer. “We had developed a substance that was supposed to reduce chronic inflammation in pathologies such as autoimmune diseases,” reports Philip Larsen, Global Head of Research and Early Development at Bayer. “The CCR1 receptor plays a role there, too. We found the substance to be very well tolerated, but unfortunately it did not have the desired effect on chronic inflammatory diseases. However, it might be helpful in the case of COVID-19, where an acute augmented immune response needs to be toned down. That is exactly what we now want to test with our colleagues at the BIH.”
In the planned multicenter CATCOVID study in which, in addition to Charité, participating study centers include University of Leipzig Medical Center, the University Hospital of Würzburg and the Unfallkrankenhaus Berlin, the therapeutic substance is now being given a second chance: Thanks to the existing study data, the scientists can start with phase II, which provides an enormous head start in terms of time. “Bayer has already begun producing the pharmaceutical formulation, so we will be able to enroll the first patients in the study in a few months,” says Eils. Professor Christopher Baum, Chair of the BIH Board of Directors and Chief Translational Research Officer of Charité – Universitätsmedizin Berlin, adds: “This is an excellent example of the rapid translation of BIH research findings into a clinical trial. And of course, we very much hope that COVID-19 patients will benefit from therapy with this drug.”
Preliminary studies at the BIH:
https://www.bihealth.org/en/notices/the-dangerous-dual-role-of-the-immune-system...
https://www.bihealth.org/en/notices/an-augmented-immune-response-explains-the-ad...
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About the Berlin Institute of Health (BIH)
The mission of the Berlin Institute of Health (BIH) is medical translation: transferring biomedical research findings into novel approaches to personalized prediction, prevention, diagnostics and therapies and, conversely, using clinical observations to develop new research ideas. The aim is to deliver relevant medical benefits to patients and the population at large. As the translational research unit within Charité, the BIH is also committed to establishing a comprehensive translational ecosystem – one that places emphasis on a system-wide understanding of health and disease and that promotes change in the biomedical translational research culture. The BIH was founded in 2013 and is funded 90 percent by the Federal Ministry of Education and Research (BMBF) and 10 percent by the State of Berlin. The founding institutions, Charité – Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), were independent, member entities within the BIH until 2020. Since 2021 the BIH has been integrated into Charité as the so-called third pillar. The MDC is now the Privileged Partner of the BIH.
https://www.bihealth.org/en/notices/bih-launches-clinical-trial-of-the-treatment...
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