Every year, 10 million people contract tuberculosis (TB), a disease caused by the bacterium Mycobacterium tuberculosis (Mtb), and approximately 1.5 million patients succumb to the disease. Treatment of TB usually requires several months of antibiotic therapy, but the rise of drug-resistant forms of TB has led to an urgent need for new drugs. The novel antibiotic BTZ-043, developed jointly by researchers at the German Center for Infection Research (DZIF), the Institute for Infectious Diseases and Tropical Medicine (Tropical Institute) at the LMU University Hospital Munich and the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI) in Jena, has shown good bactericidal activity in human clinical trials. In a study recently published in the renowned journal Nature Communications, DZIF scientists led by the University of Bayreuth and the Research Center Borstel, Leibniz Lung Center—in collaboration with Leibniz-HKI, the Tropical Institute Munich and Johns Hopkins University—made important progress in the research of this drug. They were able to show that BTZ-043 effectively penetrates TB lesions and accumulates there in high concentrations. Consequently, the drug can fight Mtb bacteria even in hard-to-reach areas.
A characteristic feature of tuberculosis (tubercle = nodular swelling) is the formation of granulomas. These nodular tissue changes are formed by the body in the lungs to wall off and contain Mtb bacteria. Granulomas are composed of a fibrous capsule which surrounds a layer of immune cells and a core of dead tissue (necrotic core) where the bacteria can hide and survive. These necrotic areas pose a particular challenge as they are poorly supplied with blood, making it difficult for antibiotics to reach them. Using a mouse model that reflects the TB pathology of granuloma necrosis in humans, the DZIF research team demonstrated the remarkable ability of the new antibiotic BTZ-043 to efficiently penetrate, accumulate and reduce the bacterial load in these necrotic granulomas.
The researchers exploited an advanced mouse model in which a genetic modification causes the development of granulomas in these animals similar to those found in TB patients. In a landmark study using these mice, recently published in Nature Communications, the researchers demonstrated that the concentration of BTZ-043 in the lesions was many times higher than the minimum concentration required to effectively combat Mtb.
High-resolution MALDI mass spectrometry also revealed the unique ability of BTZ-043 to penetrate deep into the cellular compartments of the lesions and completely penetrate the necrotic centers.
"Our study represents an important step in the development of new tuberculosis antibiotics, as we were able—for the first time—to visualize the distribution of a clinical-stageTB drug under development in the granuloma," says DZIF scientist Prof. Andreas Römpp from the University of Bayreuth, Chair of Bioanalytical Sciences and Food Analysis, first author and corresponding author of the study.
"The ability of BTZ-043 to reach and act in these hard-to-reach lesions indicates a strong bactericidal effect that could make tuberculosis therapy more efficient," adds corresponding last author and DZIF scientist Dr. Kerstin Walter from the Research Center Borstel, Leibniz Lung Center.
The development of this advanced mouse model, which in contrast to many commonly used mouse models recapitulates the pathology of human tuberculosis very well, is a milestone in the search for new antibiotics against tuberculosis," adds Dr. Christoph Hölscher, research group leader at the Research Center Borstel, Leibniz Lung Center and coordinator of the central theme "New Drugs and Regimens" in the DZIF research area "Tuberculosis".
"These findings are promising for the millions of people suffering from tuberculosis worldwide and offer a glimpse of a future in which less accessible tuberculosis lesions can be reached with another drug. As research progresses, the potential of BTZ-043 to improve clinical outcomes for tuberculosis patients becomes clearer," says Dr. Julia Dreisbach, Scientific Program Manager for BTZ-043 at the Tropical Institute Munich.
The work was funded by the Federal Ministry of Education and Research (BMBF) in the framework of the German Center for Infection Research (DZIF). The researchers would like to thank their colleagues at the Research Center Borstel, Leibniz Lung Center for organizing the animal husbandry and for their support in carrying out the experiments. Further thanks go to Hapila GmbH, Gera, who produces BTZ-043 and provides all analytical standards for the LMU University Hospital Munich and Leibniz-HKI.
Original publication: Römpp, A., Treu, A., Kokesch-Himmelreich, J. et al. The clinical-stage drug BTZ-043 accumulates in murine tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis. Nat Commun 16, 826 (2025).
Source: DZIF
Modern cancer immunotherapies are very effective, but often have severe side effects that can lead to discontinuation of therapy. Researchers at the University Medical Center Freiburg, including those from the German Cancer Consortium (DKTK), partner site Freiburg, have now shown that a special light therapy for blood cells can significantly reduce these side effects without impairing the tumor's immune response.
The so-called extracorporeal photopheresis (ECP) specifically alleviates the inflammation caused by immunotherapy. The researchers also discovered the mechanism behind it. They showed that the body's own molecule adiponectin, known from fat metabolism, regulates inflammation. The results were published in the journal Cancer Cell on February 10, 2025. The work is based on an intensive collaboration between many scientists from Freiburg, in particular the Departments of Internal Medicine I and II at the University Medical Center Freiburg, and researchers from Baltimore, USA.
“We were able to stop the side effects of cancer immunotherapy as far as possible. What is particularly exciting is that the body's defense against cancer does not suffer as a result. This significantly improves the quality of life of cancer patients,” says Prof. Dr. Robert Zeiser, Head of the Department of Tumor Immunology and Immune Regulation at the Department of Internal Medicine I at the Freiburg University Medical Center, spokesperson of the Collaborative Research Center 1479 ‘OncoEscape’ and member of the Cluster of Excellence CIBSS - Centre for Integrative Biological Signalling at the University of Freiburg. “In the future, many patients could benefit from immunotherapy for whom this has been too burdensome up to now,” says Prof. Dr. Justus Duyster, Medical Director of the Department of Internal Medicine I at the Freiburg University Medical Center.
In a clinical study with 14 patients affected by severe inflammatory side effects, ECP showed great success. 92 percent of participants reported a significant improvement in their symptoms, and all patients with inflammatory bowel disease (colitis) were completely cured. In addition, the dosage of anti-inflammatory medication such as cortisone, which often has severe side effects, was reduced in all patients.
To date, extracorporeal photopheresis has mainly been used in very specific cases in transplant medicine, for example in the treatment of graft-versus-host reactions after stem cell transplants. In this process, immune cells are removed from the patient, irradiated with UV light and returned to the body. These modified cells send out signals that calm the immune system.
Particularly surprising was the discovery that the effect of ECP is controlled by adiponectin - a molecule that was previously known primarily for its role in fat metabolism. “We were able to show that adiponectin specifically reduces pro-inflammatory cells in tissues such as the intestine without weakening the tumor defense,” says Lukas Braun, first author and molecular physician in Zeiser's research group.
“It was unexpected that a molecule from fat metabolism could influence the immune system in such a targeted way,” explains Prof. Zeiser. “This discovery could also open up new possibilities for the treatment of inflammatory diseases.”
“The ECP in combination with the knowledge about the central role of adiponectin offers new perspectives for the targeted treatment of side effects of immunotherapies,” says Zeiser. “Future studies should now confirm the results in larger patient groups and further investigate the potential of adiponectin.”
Original publication: Braun, L.M., Giesler, S., Andrieux, G. et al. Adiponectin reduces immune checkpoint inhibitor-induced inflammation without blocking anti-tumor immunity. Cancer Cell, Volume 43, Issue 2, 269 - 291.e19.
Changes in diet and the environment constantly pose new challenges to the human metabolism. Different organs and tissues work together in complex interactions to keep the metabolism in balance. The human body has a sophisticated system of inter-organ communication that allows cells to influence metabolic pathways in distant tissues. Dysregulation of these pathways contributes to a wide range of human diseases, including obesity, diabetes, lung disease, cancer, infections, liver disease, neurodegenerative diseases, mental disorders and atherosclerosis.
Two interdisciplinary projects of the German Centers for Health Research (DZG) are investigating the complex networks and mechanisms that control the metabolism with the aim of developing new therapeutic approaches.
The human body is a highly complex network of organs and tissues that communicate, exchange signals and metabolites, and influence each other. This inter-organ communication plays a crucial role in the development and treatment of disease, but is not yet fully understood. In particular, our metabolism is closely linked to inflammation, aging and chronic disease. Metabolites can circulate as signaling molecules between tissues, either promoting healing or exacerbating disease.
A new field of research is coming into focus: inter-organ metabolomics investigates which metabolic products are exchanged between organs, how they influence biological processes and what role they play in disease mechanisms. In order to better understand these interrelationships, the German Centers for Health Research (DZG) have launched the innovation fund "Inter-Organ Metabolomics". The goal is to bring together researchers from different disciplines to gain new insights across disciplinary boundaries.
Two outstanding projects have been selected for funding and will receive a total budget of up to 766.000 euros (Project 1) and 796.000 euros (Project 2) over 2025 and 2026.
Muscle loss is not only the result of immobility or malnutrition - the immune system often plays a crucial role. Certain metabolites released in serious diseases such as cancer or COPD (chronic obstructive pulmonary disease) can permanently reprogram immune cells. Instead of regulating inflammation, they promote muscle atrophy. This may play a critical role in cachexia, a syndrome that leads to muscle wasting that cannot be fully reversed even with improved nutrition.
"Our goal is to find out which metabolites alter the immune system in a way that increases muscle loss. If we understand this, we can intervene therapeutically in a targeted way," explains Dr. Maria Rohm from Helmholtz Munich, scientist at the German Center for Diabetes Research (DZD) and head of the funded project "Metabolite-mediated epigenetic changes in immune cells induce a coordinated response across tissues in cachexia".
In addition to the immune system, fat metabolism may also play a key role in cachexia. "There are indications that adipose tissue acts as an early signal transmitter in cachexia and communicates with the muscles. If we can decipher these mechanisms, we may be able to slow down or even stop the process," says Prof. Alexander Bartelt of the Technical University of Munich and scientist at the German Center for Cardiovascular Research (DZHK).
An interdisciplinary team of researchers from five of the eight German Centers for Health Research—DZD, DZHK, DZL (lung research), DZIF (infection research) and DKTK (translational cancer research)—is investigating these mechanisms. Using cell models, disease models and patient data, the researchers are analyzing which biochemical pathways control this fatal process—in the hope of developing new therapeutic approaches to combat cachexia.
"By combining metabolomics, epigenetics and immunology, we are trying to identify the mechanism of tissue communication mediated by immune cells that leads to muscle wasting in cachexia and sarcopenia," adds DZIF scientist Prof. Karsten Hiller from the Technische Universität Braunschweig.
Cardiovascular disease, cancer, COPD and diabetes are among the most common age-related diseases. A genetic change in the blood system called clonal hematopoiesis of indeterminate potential (CHIP) may play a key role. It occurs in more than 20 percent of people over the age of 65 and is associated with chronic inflammation and impaired healing processes in the heart, lung and blood vessels.
But how exactly do these genetic changes affect the immune system and communication between organs? The second funded project, "Targeting metabolic interorgan communication in inflammation-induced aging—how somatic mutations drive age-related diseases," will investigate this question.
"We have learned that genetic mutations in blood cells not only increase the risk of leukemia, but also influence inflammatory and metabolic processes in other organs," says Prof. Michael Rieger from the Frankfurt University Hospital, scientist in the German Cancer Consortium (DKTK).
"This finding opens up completely new possibilities for fighting age-related diseases at their roots," adds DZL scientist Prof. Soni Pullamsetti from the Justus Liebig University Giessen.
The interdisciplinary team of researchers from five German Centers (DKTK, DZD, DZHK, DZIF and DZL) is investigating these questions. The goal is to decipher the effects of CHIP mutations in blood cells on inflammatory processes and metabolic changes in the affected organs. These findings could make a decisive contribution to the development of new prevention and treatment strategies against age-related diseases.
The two funded projects illustrate the following: Complex disease mechanisms can only be elucidated through interdisciplinary cooperation. Researchers from cardiovascular research, pulmonary medicine, oncology, metabolic medicine and infection research are combining their expertise to answer common questions.
The DZG Innovation Fund specifically supports cooperation across specialist and institutional boundaries—with the aim of developing new approaches to the diagnosis and treatment of widespread diseases.
Project 1: “Metabolite-mediated epigenetic changes in immune cells induce a coordinated response across tissues in cachexia.”
Scientists involved:
Maria Rohm (DZD, Helmholtz Munich), Stephan Herzig (DZD, Helmholtz Munich), Ali Önder Yildirim (DZL, Helmholtz Munich), Soni Pullamsetti (DZL, Justus Liebig University Giessen), Karsten Hiller (DZIF, Technische Universität Braunschweig), Maximilian Reichert (DKTK, TUM University Hospital), Alexander Bartelt (DZHK, Technical University of Munich)
Project 2: “Targeting the metabolic interorgan communication of ‘inflamm-aging’ – how somatic mutations drive common age-associated diseases.”
Scientists involved:
Michael Rieger (DKTK, Frankfurt University Hospital), Stefanie Dimmeler (DZHK, Goethe University Frankfurt), Soni Pullamsetti (DZL, Justus Liebig University Giessen), Triantafyllos Chavakis (DZD, Technische Universität Dresden), Christoph Spinner (DZIF, Technical University of Munich)
People with prediabetes often develop diabetes, but many of them also manage to return to normoglycemia. What determines these different trajectories? And can we identify biomarkers that predict the different developments of prediabetes? To answer these questions, researchers from the Paul Langerhans Institute Dresden of the German Center for Diabetes Research (DZD), together with other experts, used the multicenter DZD study PLIS (Prediabetes Lifestyle Intervention Study). The researchers compared the proteome and metabolome signatures of prediabetes patients who showed opposite disease progressions, i.e. they focused on patients who either developed diabetes or whose blood glucose levels returned to normal over time. The results of this work have now been published in the journal Diabetes Care.
The progression of prediabetes to type 2 diabetes is associated with pancreatic beta cell dysfunction, while remission to normoglycemia is thought to be related to an improvement in insulin sensitivity. In order to understand the mechanisms and identify potential biomarkers for the possible further course of prediabetes, the researchers conducted an exploratory case-control study with participants of the PLIS study, comparing the proteomic and metabolomic profile of individuals with prediabetes who developed diabetes within one year with that of individuals who returned to normoglycemia.
The team, led by Prof Nikolaos Perakakis, analyzed 1389 proteins and 152 metabolites from plasma samples of individuals at the prediabetes stage and one year later, when some of the subjects had returned to normoglycemia while others developed diabetes. Significant differences were found in 14 proteins in new-onset diabetes compared to normoglycemia, with six of these proteins observed for the first time in this context. Elevated levels of two of the proteins, dicarbonyl/L-xylulose reductase (DCXR) and glutathione S-transferase A3 (GSTA3), at the prediabetes stage were associated with a significantly increased risk of developing diabetes one year later.
Another aspect of the study highlighted the role of inflammatory and immune system pathways in glucose homeostasis. Here, the scientists were able to show that signaling pathways related to leukocyte chemotaxis, chemokines, cytokine interactions and immune responses to infections can be associated with the progression from prediabetes to diabetes.
Metabolomic signatures in new-onset diabetes were characterized by increased levels of intermediate density lipoproteins, branched-chain amino acids, apolipoprotein A2 and glutamate. Metabolomic and proteomic signatures distinguishing between prediabetes trajectories correlated more strongly with markers of insulin sensitivity and to a lesser extent with markers of beta cell function.
“We were able to successfully identify new candidates that are associated with the progression from prediabetes to diabetes or its remission. At the same time, we were able to show that signaling pathways that regulate immune responses are strongly associated with prediabetes progression,” summarizes Prof Perakakis. “In the future, the new candidate proteins could serve as biomarkers for prediabetes progression or as targets for evaluating their role in glucose homeostasis in mechanistic studies.”
Original publication: Barovic, M., Hahn, JJ., Heinrich, A. et al. Proteomic and Metabolomic Signatures in Prediabetes Progressing to Diabetes or Reversing to Normoglycemia Within 1 Year. Diabetes Care. 2025 Mar 1;48(3):405-415.
Source: DZD
A recently launched study under the auspices of DZNE is investigating whether patients with “dementia of unclear etiology” benefit from examination of their brains using amyloid positron emission tomography (amyloid PET). Should this form of diagnostics contribute significantly to a better disease progression, the statutory health insurance providers could possibly pay for such brain scans in the future. The study was commissioned by the Federal Joint Committee (G-BA), the body that decides on the services covered by German statutory health insurers.
Every year, more than 350,000 people in Germany develop dementia. Whether this is due to Alzheimer’s or another neurological disease often remains unclear. “Diagnostic uncertainty prevents the best possible treatment. Although there is currently no cure for dementia, there are specific therapeutic measures depending on the form of dementia that support the capacity to independently manage activities of daily living. This is important for the quality of life of patients,” explains Prof. Stefan Teipel, dementia researcher at the DZNE’s Rostock/Greifswald site and head of the Section for Gerontopsychosomatics and Dementia at Rostock University Medical Center. “With this in mind, we investigate whether amyloid PET can help provide good care for people with dementia.”
Amyloid PET can detect so-called amyloid in the brain. These protein deposits are hallmarks of Alzheimer’s and thus provide important evidence for diagnosis. It was shown that this technique increases diagnostic certainty. But does it provide added value for patients? In fact, such benefit has not been clearly demonstrated so far, which is why this examination is generally not covered by statutory health insurance providers in Germany. The current research project named “ENABLE: Patient- and care-related benefits of amyloid PET imaging” (a study according to §137e of the German Social Code Book V) aims to provide certainty. The criterion is how the study participants’ everyday skills develop as a consequence of PET examination and subsequent therapy. The project is financed by the “Federal Joint Committee”, a central body in the German healthcare system. “Our study results will be considered in future decisions on the services provided by statutory health insurance companies,” says study leader Stefan Teipel.
Under the lead of DZNE, more than 20 study centers across Germany located at university hospitals as well as institutions from the private practice sector will participate in the investigation. “After several years of preparation, we have now enrolled the first subjects in the study. By 2026, we aim to include more than a thousand individuals with mild to moderate dementia of unclear cause, all of whom being treated within the framework of regular care,” says Teipel.
Prof. Gabor Petzold, DZNE’s Director of Clinical Research, sees this study as a prime example of cooperation between research and clinical practice: “Partners from academia, industry and healthcare are involved in this project. This way, we are building a bridge between research and practice. This study will provide important momentum for the health care of people with dementia in Germany.”
The study participants will be randomly assigned to two equally sized groups: The subjects in one group will be examined with amyloid PET, while the others will not. This will only include patients in whom the alternative procedure for detecting amyloid (which involves taking a fluid sample from the spinal canal) could not be performed or did not provide a conclusive result. “The PET findings will have an impact on medication and other therapeutic measures. The question now is whether this has measurable consequences. That is, if these people are better able to cope with everyday life than those in the control group who did not have a PET scan,” says Teipel. “That is why we will monitor the development of the daily living skills of all study participants over a period of 24 months.”
Source: DZNE
The VADYS-ME research project is investigating how vascular problems and circulatory disorders could trigger symptoms such as extreme fatigue and concentration problems in patients with ME/CFS - with the aim of developing better diagnostic and therapeutic options.
The aim of the project is to better understand the causes and mechanisms of this debilitating disease and to develop new approaches for diagnosis and treatment. The project is headed by Prof. Wolfram Döhner, MD, scientist at the Berlin Institute of Health (BIH) and the German Heart Centre at Charité - Universitätsmedizin Berlin, partner of the German Centre for Cardiovascular Research (DZHK).
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) leads to a severe reduction in physical and mental performance. Those affected often suffer from extreme exhaustion, muscle weakness and concentration problems. The disease occurs after infectious diseases, and a significant increase in frequency has been observed, particularly after the COVID pandemic. Other viral diseases such as the Epstein-Barr virus (EBV), which is responsible for glandular fever, as well as influenza or other respiratory infections are also associated with the development of ME/CFS.
This joint project, VADYS-ME, is investigating whether and how disturbances in the regulation of the blood vessels and blood supply affect the metabolism and thus the function of tissues and organs. This in turn can contribute to typical symptoms such as muscular weakness, generalised fatigue and concentration disorders.
Imaging techniques such as magnetic resonance imaging are used to analyse how well the brain, heart and muscles are supplied with blood. The metabolism of the skeletal muscles is also analysed and blood samples from ME/CFS patients are examined specifically for certain characteristics (‘biomarkers’) of the regulation of blood flow.
The VADYS-ME research project is being carried out by Charité in cooperation with the Technical University of Munich (project leader Prof Dr Schmaderer) and is being funded by the Federal Ministry of Education and Research (BMBF) with 2.6 million euros. It brings together the expertise of five research teams from Charité, including the Berlin Institute of Health (BCRT), the German Heart Centre Berlin, the Department of Neurology at Charité and the Experimental and Clinical Research Center (ECRC), as well as the Technical University of Munich. Patient organisations (Lost Voices Foundation and the ME/CFS Research Foundation) have also been involved in the project from the outset in order to incorporate the perspective of patients and sufferers into the clinical research work.
Professor Wolfram Döhner, MD, who is leading the project, explains: ‘With VADYS-ME, we want to better understand the mechanisms of ME/CFS and look for new methods to make a reliable and rapid diagnosis and also open up opportunities for new treatments to ultimately improve patients’ quality of life.’
Source: DZHK
The interdisciplinary project DEFENDER is developing innovative approaches to combat (re-)emerging viruses. The project, coordinated by the Leibniz Institute of Virology (LIV), is being funded with around 9.6 million euros as part of Horizon Europe. Almost 700,000 euros of these will go to Prof. Mark Brönstrup, a researcher at the Helmholtz Centre for Infection Research (HZI) and the German Center for Infection Research (DZIF).
The COVID-19 pandemic has highlighted the immense risk potential posed by (re‑)emerging viruses. There are neither approved vaccines nor specific therapies for many of these viruses. This is precisely where DEFENDER (iDEntification oF novel viral Entry factors aNd DevelopmEnt of antiviRal approaches) comes in: The project aims to develop new, alternative antiviral approaches in order to be prepared for future outbreaks.
By using state-of-the-art technologies such as CRISPR gene technology, bioinformatic analyses and artificial intelligence, DEFENDER is pursuing an integrated concept for the development of new targets for antiviral therapies that focuses on both the host and the virus. On the host side, new host factors are identified that play a key role in viral entry, while on the virus side, virus structures are identified that represent potential targets for therapeutic antibodies or nanobodies.
The research focus of the DEFENDER consortium lies on highly pathogenic viruses such as the Nipah and Lassa viruses as well as viruses transmitted by mosquitoes that cause Zika, dengue, yellow fever and chikungunya.
Starting on January 1, 2025, DEFENDER will run for five years and will make a decisive contribution to improving European and global pandemic preparedness. Systematic research into virus-host interactions will be used to develop antiviral candidates that can be followed up in clinical trials.
Project leader Prof. Stephanie Pfänder (Research Group Emerging Viruses, LIV) emphasises: “DEFENDER combines the expertise of leading European research institutions in the fields of virology, structural biology, genetics and bioinformatics to develop innovative, forward-looking antiviral strategies.We are convinced that we will make a significant contribution to combating future virus outbreaks.“
Prof. Mark Brönstrup, head of the Department “Chemical Biology” at the HZI and scientist in the Novel Antibiotics research area of the DZIF, adds: “We are happy to contribute our expertise in antiviral drug conjugates such as PROTACs to DEFENDER to validate new therapeutic concepts against emerging pathogens.”
In addition to the LIV and the HZI, ten other institutions are involved in DEFENDER: The University of Zurich (Switzerland), Greifswald University Medicine (Germany), Universität zu Lübeck (Germany), École Polytechnique Fédérale de Lausanne (Switzerland), Heidelberg University (Germany), Liverpool School of Tropical Medicine (England), Institut Pasteur (Paris, France), Ruhr University Bochum (Germany), Phillips-Universität Marburg (Germany) and the Bernhard Nocht Institute for Tropical Medicine (Hamburg, Germany).
Source: DZIF
The DZPG researches mental health in the context of the ecological crisis - Climate change leads to psychological stress. There are several reasons for this: Firstly, there is the fear of an uncertain future with considerable uncertainties, loss of prosperity and distribution struggles. Secondly, more and more people are personally affected by extreme weather events such as those in the Ahr Valley. Thirdly, environmental problems such as increasing heat and air pollution are affecting people not only physically but also emotionally. DZPG spokespersons Professor Andreas Heinz and Professor Andreas Meyer-Lindenberg name ways out: the DZPG wants to better research the interaction between the environment and mental health and develop new treatment and prevention approaches on this basis.
Research into the psychological effects of environmental problems is far from starting from scratch. We know that “natural disasters are associated with an increase in depression, anxiety and trauma-related disorders,” says DZPG spokesperson Meyer-Lindenberg. This increase can be observed above all in areas where many people are directly affected by a disaster such as flooding, such as recently in the Ahr valley, Saarland or Bavaria, but also beyond. This has been well researched in the aftermath of Hurricane Katrina, for example.
In addition to trauma-related disorders, there are indirect consequences of climate change such as food shortages, economic crises, violent conflicts and involuntary migration. These are also psychological risk and stress factors that can lead to uncertainty and anxiety before they occur and to trauma afterwards.
In addition to these two factors, the consequences of the current ecological crisis are compounded by grief over the loss of an intact environment (“solastalgia”) and fear of an uncertain future, also known as “climate anxiety”. DZPG spokesperson Andreas Heinz explains: “Humanity is not only faced with the problem of global warming and its consequences. There is also the loss of biodiversity, the plastic crisis in the oceans, overfishing, over-fertilization of the soil and the poor condition of the forests. No matter where we look: They see the destruction of habitats that in the past could offer carefree experiences of nature. This makes it difficult to relax and puts a strain on the soul, and this is where we at the DZPG must continue our research: What increases resilience? Who is particularly at risk?” Without prevention and effective tools against the psychological consequences of environmental degradation, there is a risk of considerable economic damage due to mental illness.
There are also still questions regarding care. “Even if symptoms such as anxiety disorders are often easily treatable: The basic problem, the state of the environment, is not a traumatic experience in the past, but a rational concern,” explains Andreas Heinz. Because unlike a violent childhood, for example, which those affected can leave behind, the destruction of the environment does not stop; spatial or temporal distance are not available as therapeutic aids.
However, you are not at the mercy of your feelings even today, says Meyer-Lindenberg. One way can be to increase your own “ecological handprint” and become aware of your scope for action. “Meaningful work or voluntary work that counteracts the environmental crisis and a way of life that doesn't ignore the problems of the present can be an effective step against despair.” Although the environmental crisis cannot be solved single-handedly, trying to counteract the environmental crisis with your own behavior and energy can increase your own mental resilience.
The WHO's One Health approach examines the connections between humans, animals, plants and their shared environment. While this currently focuses on physical health, the DZPG is extending this concept to mental health and will conduct better research into the interaction with the environment and develop new treatment and prevention approaches on this basis. The linchpin of the research activities is the One Mental Health Hub, which is scheduled to be founded in 2025.
Source: DZPG
A nationwide research consortium led by the University Hospital Schleswig-Holstein (UKSH) and the Medical Faculty of the Christian-Albrechts-University of Kiel (CAU) has received €4.9 million in funding for the COVIDOM+ study. The aim is to investigate the long-term effects of a SARS-CoV-2 infection, particularly Post-COVID Syndrome (PCS), in comparison to other respiratory diseases.
The involved institutions are part of the Airway Research Center North (ARCN) of the German Center for Lung Research (DZL). In collaboration with the University Hospital Würzburg and Charité – Universitätsmedizin Berlin, participants from various regions of Germany – including Schleswig-Holstein, Bavaria, and Berlin – will be followed over several years to analyze the long-term effects of COVID-19, especially PCS.
The COVIDOM+ study builds on the ongoing COVIDOM cohort since 2020 and investigates how frequently and severely PCS occurs and how it differs from other post-infectious diseases such as ME/CFS. Typical symptoms like chronic fatigue, concentration difficulties ("brain fog"), or breathing problems will be analyzed. The psychological and potentially age-related effects of COVID-19 are also in focus.
“The follow-up study COVIDOM+ will help us better understand the frequency, severity, and long-term effects of Post-COVID Syndrome. We aim to determine how factors such as the timing of infection, vaccination status, disease course, and pre-existing conditions influence the development of PCS and identify different manifestations, known as phenotypes, while distinguishing them from other post-infectious diseases like chronic fatigue syndrome,” explains Prof. Dr. Jan Heyckendorf, DZL scientist, Director of the Department of Internal Medicine I at UKSH, Campus Kiel, and project leader of COVIDOM+. “The insights gained will contribute to the development of clinical guidelines and improve the care of affected individuals through more precise diagnostic and treatment approaches,” adds PD Dr. Thomas Bahmer, also a DZL scientist and co-study leader of COVIDOM+.
COVIDOM+ is funded by the Federal Ministry of Health (BMG) with €4.9 million for the years 2025 and 2026. The results aim to improve the care of patients with Post-COVID Syndrome and other long-term effects.
Source: DZL
A groundbreaking study by scientists at the LMU Hospital Munich and the German Centre for Cardiovascular Research has shown that antibodies and the complement system play central roles in the development of thrombosis. This discovery could lead to new treatment strategies that do not involve the bleeding risk of conventional anticoagulants.
Venous thromboembolism (VTE) is a life-threatening blood clot which its frequency is increasing worldwide despite preventive measures. The role of antibodies in immune defence has long been known, but this study brings surprising new findings: IgM and IgG antibodies, regardless of their specificity to a particular antigen, promote the formation of blood clots.
IgM antibodies bind to endothelial cells that line the blood vessels and activate them, which triggers the accumulation of platelets. This phase is the first step in the formation of a thrombus. IgG antibodies then attach to activated platelets and trigger the complement system, which initiates a cascade of biochemical processes that intensify thrombosis formation through inflammatory processes.
‘Our study shows that antibodies and the complement system play a previously underestimated role in the development of thrombosis, regardless of which antigens the antibodies recognise,’ explains Prof. Konstantin Stark, Senior Consultant in Cardiology at the LMU Hospital in Munich and author of the study.
IgM and IgG are reffered to as two of the most important antibodies in the human immune system. IgM antibodies are the first to be produced after an infection and play a decisive role in the initial defence against pathogens. They are particularly efficient in neutralising bacteria and viruses and in activating the complement system. IgG antibodies are the most abundant antibodies in the blood and are responsible for long-term immunity. They mark pathogens so that they can be more easily recognised and eliminated by immune cells.
However, the present study showed that these antibodies not only contribute to immune defence, but can also trigger and promote thrombosis. It is particularly noteworthy that this process occurs independently of the antigen specificity of the antibodies, which means that the antibodies exert their prothrombotic effects without having to recognise a specific antigen.
One of the most important discoveries of the study shows that the targeted inhibition of the complement system can prevent thromboses. In contrast to conventional blood thinners, which often increase the risk of severe bleeding, natural blood clotting remains unaffected. The researchers found that this blockade is not only safer, but also effectively reduces thrombosis.
‘This method offers a promising new approach to prevention of thrombosis, which prevents the formation of blood clots without increasing the risk of bleeding,’ explains Prof Stark.
The study results not only have an impact on the treatment of venous thrombosis, but also affect other diseases in which the complement system is involved.The parallels between thrombosis development and the thrombotic complications observed in severe COVID-19 cases are of particular scientific interest. In the autopsy samples from COVID-19 patients, the researchers found the same prothrombotic mechanisms as in their animal models: Antibodies and the complement system worked together to promote the formation of blood clots.
These findings could also play a role in the treatment of other immune-mediated thromboses, such as antiphospholipid syndrome. In addition, inhibition of the complement system could play a key role in the future in the treatment of thrombotic complications triggered by vaccines or antibody therapies, as it has been reported regarding COVID-19 vaccines.
The possibility of specifically inhibiting the complement system without increasing the risk of bleeding could be particularly important for patients who have a high risk of both thrombosis and bleeding.
‘We are still at the beginning of clinical research of these new therapeutic approaches, but our results offer a promising perspective in the prevention of thrombosis,’ concludes Prof Stark. ‘Our research shows that we can pursue new approaches that primarily target the immune response in order to effectively and safely prevent thrombosis.’
Original publication: Antibodies and complement are key drivers of thrombosis. et al. Immunity. 2024 Sep 10;57(9):2140-2156.e10.
Source: DZHK
Researchers from Helmholtz Munich and Ludwig-Maximilians-Universität (LMU) have identified a mechanism that may explain the neurological symptoms of Long COVID. The study shows that the SARS-CoV-2 spike protein remains in the brain’s protective layers, the meninges, and the skull’s bone marrow for up to four years after infection. This persistent presence of the spike protein could trigger chronic inflammation in affected individuals and increase the risk of neurodegenerative diseases. The team, led by Prof. Ali Ertürk, Director at the Institute for Intelligent Biotechnologies at Helmholtz Munich, also found that mRNA COVID-19 vaccines significantly reduce the accumulation of the spike protein in the brain. However, the persistence of spike protein after infection in the skull and meninges offers a target for new therapeutic strategies.
A novel AI-powered imaging technique developed by Prof. Ali Ertürk’s team provides new insights into how the SARS-CoV-2 spike protein affects the brain. The method renders organs and tissue samples transparent, enabling the three-dimensional visualization of cellular structures, metabolites, and, in this case, viral proteins. Using this technology, the researchers uncovered previously undetectable distributions of spike protein in tissue samples from COVID-19 patients and mice.
The study, published in the journal Cell Host & Microbe, revealed significantly elevated concentrations of spike protein in the skull’s bone marrow and meninges, even years after infection. The spike protein binds to so-called ACE2 receptors, which are particularly abundant in these regions. “This may make these tissues especially vulnerable to the long-term accumulation of spike protein,” explains Dr. Zhouyi Rong, the study’s first author. Ertürk adds, “Our data also suggest that persistent spike protein at the brain’s borders may contribute to the long-term neurological effects of COVID-19 and Long COVID. This includes accelerated brain aging, potentially leading to a loss of five to ten years of healthy brain function in affected individuals.”
The Ertürk team discovered that the BioNTech/Pfizer mRNA COVID-19 vaccine significantly reduces the accumulation of spike protein in the brain. Other mRNA vaccines or vaccine types, such as vector- or protein-based vaccines, were not investigated. Mice vaccinated with the mRNA vaccine showed lower levels of spike protein in both brain tissue and the skull’s bone marrow compared to unvaccinated mice. However, the reduction was only around 50%, leaving residual spike protein that continues to pose a toxic risk to the brain. “This reduction is an important step,” says Prof. Ertürk. “Our results, while derived from mouse models and only partially transferable to humans, point to the need for additional therapies and interventions to fully address the long-term burdens caused by SARS-CoV-2 infections.” Furthermore, additional studies are needed to evaluate the relevance of these findings for Long COVID patients.
Globally, 50 to 60 percent of the population has been infected with COVID-19, with five to ten percent experiencing Long COVID. This sums up to approximately 400 million individuals who may carry significant amounts of spike protein. “This is not just an individual health issue – it is a societal challenge,” says Prof. Ertürk. “Our study shows that mRNA vaccines significantly reduce the risk of long-term neurological consequences and offer crucial protection. However, infections can still occur post-vaccination, leading to persistent spike proteins in the body. These can result in chronic brain inflammation and an increased risk of strokes and other brain injuries, which could have substantial implications for global public health and healthcare systems worldwide."
“Our findings open new possibilities for diagnosing and treating the long-term neurological effects of COVID-19,” says Ertürk. Unlike brain tissue, the skull’s bone marrow and meninges – areas prone to spike protein accumulation – are more accessible for medical examinations. Combined with protein panels – tests designed to detect specific proteins in tissue samples – this could allow for the identification of spike proteins or inflammatory markers in blood plasma or cerebrospinal fluid. “Such markers are critical for the early diagnosis of COVID-19-related neurological complications,” Ertürk explains. “Additionally, characterizing these proteins may support the development of targeted therapies and biomarkers to better treat or even prevent neurological impairments caused by COVID-19.”
Highlighting the broader impact of the study, leading Helmholtz Munich and Technical University of Munich virologist Prof. Ulrike Protzer adds: “Given the ongoing global impact of COVID-19 and the increasing focus on long-term effects, this study, which sheds light on brain invasion pathways and unexpected long-term host involvement, is timely. These critical insights are not only scientifically significant but also of great interest to society.”
Original publication: Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19. Rong, Z., Mai, H., Ebert, G. et al. 2024. Cell Host & Microbe.
Source: Helmholtz Munich
Special mutations in important protective proteins lead to the proteins being broken down longer and therefore faster. This results in an increased risk of tumor growth. These findings offer new approaches for cancer therapies.
Cancer researchers from the Faculty of Medicine at the University of Freiburg have discovered that certain “non-stop mutations” make important protective proteins against cancer in the body longer, making them “water-shy”. The proteins then become more unstable in the aqueous environment of the cell, are broken down more quickly and can ultimately no longer act effectively against uncontrolled cell growth. This can increase the risk of tumors. The results of the study, which were published in the journal Nature Communications on October 25, 2024, could increase precision in the selection of suitable cancer therapies.
“We were able to show that so-called non-stop mutations can play a major role in the development of cancer. Until now, these changes have been overlooked because they do not affect the basic structure of important proteins,” says study leader Prof Dr Sven Diederichs, who heads the Department of Oncological Research in the Department of Thoracic Surgery at the Freiburg University Medical Center and is a scientist at the Freiburg partner site of the German Consortium for Translational Cancer Research (DKTK). “These findings now offer the possibility of integrating these mutations into cancer treatment decisions,” said Diederichs.
Proteins are important building blocks in our cells and are produced as a chain of molecules according to the blueprint in our genome. The end of such a blueprint is normally formed by a stop signal that ends the sequence of protein building blocks. In the case of a non-stop mutation, this stop signal is lost, so that the protein becomes longer than necessary.
Diederichs' research team has now analyzed 2,335 cases in which these non-stop mutations occurred in various types of cancer in a high-throughput screening. Using a technique called “flow cytometry”, they measured how high the concentration of the extra-long proteins was in the cells. It turned out that more than half of these proteins were degraded before they could do their job.
“We were able to show that the proteins in which the elongation makes them more water-repellent, one could also say water-shy, are more unstable in the aqueous environment of the cell. As a result, they are quickly disposed of by the cell's cleaning system. This means they can no longer fulfill their function,” explains Diederichs.
Tumor suppressor genes and the resulting proteins were particularly affected. These normally prevent the growth of tumors. “These proteins are like the safety brakes in our cells. They ensure that cells only divide when they need to and stop growth if something goes wrong. If these proteins do not function properly, cells can grow uncontrollably and develop into tumors,” says Diederichs.
In the next step, the Freiburg researchers want to further investigate the mechanisms behind the mutations, which have been largely overlooked to date. “On the one hand, we want to understand in more detail how the individual mutations work. On the other hand, we want to test whether the targeted stabilization of the affected proteins could be a basis for new therapeutic approaches,” hopes Diederichs.
Original publication: Suppressive cancer nonstop extension mutations increase C-terminal hydrophobicity and disrupt evolutionarily conserved amino acid patterns. Ghosh, A., Riester, M., Pal, J. et al. Nat Commun 15, 9209 (2024).
Source: DKTK