Misdirected Immune Responses in the Spotlight
Bonn, August 26, 2022. Experts from DZNE are participating in a new research alliance in Germany that aims to investigate the causes of “Myalgic Encephalomyelitis/Chronic Fatigue Syndrome” (ME/CFS) in the wake of infectious diseases such as COVID-19 and to contribute to better diagnostic and therapeutic options. The overall project is led by Charité – Universitätsmedizin Berlin and funded by the German Federal Ministry of Education and Research (BMBF) with approximately 2.1 million euros. The subproject coordinated by DZNE will take a close look at deviations in white blood cells – these cells are essential components of the immune system.
According to estimates, around 300,000 individuals in Germany are affected by ME/CFS, including about 40,000 young people under the age of 18. In addition to chronic fatigue, their symptoms often include muscle pain and neurological complaints, such as memory disorders. Many patients have considerable difficulty coping with everyday life. “This clinical picture has been known for decades, but the causes are largely unknown. As a result, although there are attempts of alleviating some of the symptoms, there is no effective therapy at the moment,” says Dr. Anna Aschenbrenner, group leader in systems medicine at DZNE in Bonn. “ME/CFS is known to occur after serious infections, for example, in the aftermath of mononucleosis, herpes infection or COVID-19. As a result of the COVID-19 pandemic, the number of cases is expected to increase significantly. These fall within the spectrum of complaints referred to as Long-COVID.”
Immune System on the Wrong Track?
Findings suggest that ME/CFS patients develope a dysfunction of the immune system contributing to many of the symptoms. The members of the nationwide research network will investigate various aspects of this hypothesis. “In our subproject, we plan to take a detailed look at the white blood cells of patients who are affected by ME/CFS and have previously sustained mononucleosis, COVID-19 or other infections,” Aschenbrenner explains.
Wanted: Markers ...
In order to assess the status of the immune cells, the team of the Bonn scientist is using highly sensitive techniques. “Among other things, we will analyze the so-called transcriptome. This is a molecular signature from which it is possible to deduce how an immune cell is doing and whether it is healthy or whether there are dysfunctions,” says Aschenbrenner. “As transcriptome data is complex, we will use sophisticated computational approaches for the analysis. By doing so, we hope to find patterns in the data that are typical of ME/CFS.” In this way, the researchers intend to establish a link between clinical symptoms and events at the cellular level. “Currently, ME/CFS can only be diagnosed laboriously on the basis of symptoms. So far, there are no laboratory parameters that can be used to identify the clinical profile of the disease. Such biomarkers would greatly simplify diagnosis.“
... and Therapeutic Approaches
Identifying such markers is an important goal of the Bonn research project, led by Anna Aschenbrenner in collaboration with Joachim Schultze (DZNE) and Leif Erik Sander (Charité). Another is to find approaches for therapy. “If we can tell from our data if there are dysfunctions in the immune cells and what these consist of, this opens up the possibility of doing something about them. For this, we want to identify drug candidates,” says Aschenbrenner. In the sense of so-called drug repurposing, this involves already approved compounds that have so far been used in a different context. “The advantage of this approach is that such drugs are already known to be safe and tolerable in principle. Therefore, they reach patients more quickly than if a new drug had to be developed and tested over many years. We aim to contribute to this with our research.“