Research

Project Details:
Roundworms of the genus Toxocara can infect humans and persist in tissues for years or decades. Although the parasite cannot complete its life cycle, the infective larvae migrate through the body and can reach various organs, and thus cause considerable health damage. To characterise the zoonotic risk by roundworms, studies are being conducted on environmental contamination, human infections and evaluation of diagnostic tools. At the level of parasite-host interaction, in addition to immunological interactions, neurological damage in the host as a result of roundworm infection is also being characterised. Thus, not only larval distribution in the entire body of the host, but also the distribution of larvae and resulting damage in the brain is investigated. Here, neuropathological changes and gene regulation in the paratenic host are assessed by histopathology, molecular biological methods and behavioural studies.

Results:

Waindok, P., Janecek-Erfurth, E., Lindenwald, D. L., Wilk, E., Schughart, K., Geffers, R., Strube, C. (2022) Toxocara canis- and Toxocara cati-induced neurotoxocarosis is associated with comprehensive brain transcriptomic alterations. Microorganisms 10, 177

 

Waindok, P., Kann, S., Aristizabal, A., Dib, J. C., Strube, C. (2021) Toxocara seroprevalence and risk factor analysis in four communities of the Wiwa, an indigenous tribe in Colombia. Microorganisms 9, 1768

 

Raulf, M.-K., Lepenies, B., Strube, C. (2021) Toxocara canis and Toxocara cati somatic and excretory-secretory antigens are recognised by C-type lectin receptors. Pathogens 10, 321

 

Waindok, P., Raulf, M. K., Springer, A., Strube, C. (2020) The zoonotic dog roundworm Toxocara canis, a worldwide burden of public health. In: Strube C., Mehlhorn H. (Hrsg.) Dog Parasites Endangering Human Health. Parasitology Research Monographs, Band 13. Springer, Cham, Schweiz. S. 5-26

 

Strube, C., Waindok, P., Raulf, M. K., Springer, A. (2020) Toxocara-induced Neural Larva Migrans (neurotoxocarosis) in rodent model hosts. Advances in Parasitology 109, 189-218

 

Strube, C., Raulf, M. K., Springer, A., Waindok, P., Auer, H. (2020) Seroprevalence of human toxocarosis in Europe - a review and meta-analysis. Advances in Parasitology 109, 375-418

Cooperation Partners:

Prof. Dr. G. Gerold, Medizinische Universität Innsbruck, Österreich

Prof. Dr. B. Lepenies, Ludwig-Maximilians-Universität München

Prof. Dr. M. Pfeffer, Universität Leipzig

Dr. S. Kann, Missionsärztliches Institut Würzburg

Prof. Dr. M. Leschnik, Veterinärmedizinische Universität Wien, Österreich

Funding: Gesellschaft für Kynologische Forschung, Hahn-Stiftung, DFG, DAAD, 30.000 EUR

Project Details:
Die Untersuchung des Liquor cerebrospinalis ist ein wertvolles Instrument, um in vivo Informationen über den Zustand des zentralen Nervensystems zu erhalten. Die darin enthaltenen Zellen reflektieren zumindest teilweise die perivaskuläre Zellpopulation im ZNS. Es wurde daher eine Methode entwickelt, diese Zellen mit Hilfe der Durchflusszytometrie zu charakterisieren. Derzeit werden die Toll-like Rezeptoren näher bestimmt.
In einer 2. Studie wird untersucht, wie sich die Glukose im Liquor cerebrospinalis des Hundes verhält, und ob die Bestimmung von dieser zur Diagnostik beitragen kann oder sich proportional zur Zellzahl bzw. zur Blutglukose verhält.
In weiteren Studien werden verschiedene Biomarker, wie Tau-Protein, Chemokine, Zytokine und Abbauprodukte von Gliazellen und Nervenzellen untersucht, um einen prognostischen Faktor für Rückenmarkserkrankungen zu erhalten. Neue Methoden zur Haltbarmachung der Zellen werden evaluiert. Zusätzlich werden verschiedene Proteine auf ihre Eigenschaft als Biomarker geprüft (ApoE) und IL21.

Funding: teilweise BMBF (Lichtenbergstipendium); Gesellschaft für Kynologische Forschung; Irene und Hans-Joachim Hahn-Stiftung, DAAD, 80.000 EUR

Project Details:
Die steril-eitrige Meningitis-Arteriitis des Hundes (SRMA)ist die häufigste entzündliche Erkrankung des zentralen Nervensystems des Hundes im Norddeutschen Raum. Mit Hilfe mehrerer Pathogenesestudien soll versucht werden, die Erkrankung besser zu charakterisieren, um neue Therapiestrategien entwickeln zu können. Die Zellpopulation in Liquor cerebrospinalis und Blut wurde mit Hilfe durchflusszytometrischer Studien charakterisiert. Studien zur Zytokinexpression sollen helfen, das Phänomen der hohen IgA Produktion zu erleuchten. Die Untersuchung von Toll-like Rezeptoren soll einen Hinweis auf die Ätiologie der Erkrankung liefern. Die Th17 Antwort, NETs und das Endocannabinoidsystem werden näher untersucht.
derzeit laufen Studien, ob IL 21 und ApoE in Kombination mit akute Phase Proteinen von Bedeutung sind. Es wird untersucht, ob IL 21 für neue therapeutische Interventionen eignet.

Results:

Arianna Maiolini, Regina Carlson, M. Schwartz, G. Gandini and Andrea Tipold: "Determination of immunoglobulin A concentrations in the serum and cerebrospinal fluid of dogs: An estimation of its diagnostic value in canine steroid-responsive meningitis-arteritis." The Veterinary Journal, 191, 219-224, 2012

 

S.A. Moore, M.Y. Kim, Arianna Maiolini, Andrea Tipold and M.J. Oglesbee: "Extracellular hsp70 release in Canine Steroid Responsive Menintis-Arteritis." Vet Immunol Immunopathol., 145, 129-133, 2012

 

Arianna Maiolini, Regina Carlson and Andrea Tipold: "Toll-like receptors 4 and 9 are responsible for the maintenance of the inflammatory reaction in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis." J Neuroinflammation 9, 226 (1-12), 2012.

 

Arianna Maiolini, M. Otten, M. Hewicker-Trautwein, R. Carlson and Andrea Tipold: "Interleukin-6, vascular endothelial growth factor and transforming growth fator beta 1 in canine steroid responsive meningitis-arteritis." BMC Veterinary Research, 9:23, 1-10, 2013.

 

J. Freundt-Revilla, A. Maiolini, R. Carlson, M. Beyerbach, K. Rentmeister, T. Flegel, A. Fischer and Andrea Tipold: "Th17 skewed immune response and cluster of differentiation 40 ligand expression in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis." J. Neuroinflammation 14:20, 2017. doi.10.1186/s12974-016-0784-3.

 

J.C. Wohlsein, M. Meurer, M. Mörgelin, J.N. Nessler, T. Flegel, H. Schenk, K. Jurina, K. Rentmeister, A. Fischer, T. Gödde, W. Baumgärtner, M. v.Köckritz-Blickwede and Andrea Tipold: "Neutrophil extracellular traps in CSF and serum of dogs with steroid-responsive meningitis-arteritis." Plos One 19(1):e0295268, 2024

Funding: QS-Wissenschaftsfonds, vertreten durch die Qualität und Sicherheit GmbH, Bonn, 37.272 EUR

Project Details:
Animal health data from German cattle farming provide a foundation for the development of a benchmarking system. However, the joint analysis of these data reveals significant data gaps resulting from differing reporting obligations and varying reporting behavior of farms depending on animal group (e.g., beef cattle, dairy cows, etc.) and region. In order to enable a complete and representative assessment of animal health, these gaps must be addressed using appropriate imputation methods.The underlying data originate from cattle-keeping member farms of Qualität und Sicherheit GmbH for the years 2023 and 2024. They include information from the areas of biosecurity, animal husbandry, antibiotic use, and slaughter findings. For a comprehensive evaluation, it is necessary to consider these data areas jointly and to analyze them systematically in order to develop robust indicators for animal health benchmarking.

Cooperation Partners:

Qualität und Sicherheit GmbH, Bonn

Funding: GDK - Gemeinschaft Deutscher Kryobanken, 5.000 EUR

Project Details:
In animal breeding and biodiversity conservation programs, the use of cryopreserved sperm is becoming increasingly important. Routinely, frozen semen is stored and shipped in liquid nitrogen, which has drawbacks due to its classification as dangerous good and transport costs associated with using (disposable) cryo-containers. Cryopreservation in liquid nitrogen allows for long-term storage, however, this requires bulky ultra-low temperature freezers and/or liquid nitrogen tanks. The latter is associated with high energy-demands and costs, and leaves a large carbon-footprint. If sperm could be preserved at elevated subzero temperatures, e.g., at -80 or -70 °C, without losing their viability, this would make storage and transport easier (e.g., transport on dry ice). Therefore, there is an interest in alternative options for storing and transporting cryopreserved semen, i.e., without the need for liquid nitrogen. The stability of cryopreserved specimens, and minimum storage temperature, can be increased by adding compounds that modulate the glass transition and/or ice (re)crystallization temperature of the freezing formulation. Examples of compounds with such properties are protein and sugar polymers, like polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyvinyl alcohol (PVA) and Ficoll. In addition to increasing storage stability at elevated subzero temperatures, some polymer additives in freezing media inhibit ice recrystallization during warming.

Project Details:
The aim of our project is to investigate the regulation of key signaling pathways involved in lipid metabolism in growing goats under varying nitrogen (N) and phosphorus (P) supply. The focus lies on the INSR-Akt-mTOR and AMPK-LKB1 signaling axes, as well as on FGF21 and PPARγ as central regulators of lipogenesis, lipolysis, and energy homeostasis. In addition, we analyze the role of vitamin D, leptin, CaSR, FGFR1c, and β-Klotho receptors in adipose tissue. A total of 28 young goats are assigned to four dietary groups (control, N-reduced, P-reduced, and combined N- and P-reduced). RNA and proteins are isolated from different adipose depots, and the expression of selected target genes is analyzed by qPCR, while protein abundance is assessed by Western blotting. Metabolic plasma parameters (e.g., glucose, insulin, leptin, calcium, phosphate, and amino acids) are included in the evaluation.

By combining molecular analyses with physiological data, this project aims to clarify how different N and P supplies modulate lipid metabolism and energy-dependent signaling pathways. The study contributes to a better understanding of metabolic adaptation mechanisms in ruminants under nutrient-restricted feeding conditions.

Funding: Fritz-Ahrberg-Stiftung, 50.000 EUR

Project Details:
Basidiomycota have increasingly entered the focus of food science and industry in the last years. During their growth, they secrete a variety of lysing and redox-active enzymes and bioactive compounds that positively influence the aroma profile of inoculated foods. Therefore, their potential for the refinement of beef during dry-aging is to be evaluated in this project.

Project Details:
The Chernobyl nuclear disaster of April 1986 released significant radioactive contamination by means of radionuclides across Europe, presenting unprecedented challenges to environmental, radiochemistry, human and veterinary medicine. Among the most effective countermeasures developed was ammonium iron hexacyanoferrate, a Prussian blue compound that efficiently binds radiocesium in the digestive tract of animals. This compound prevented the absorption and bioaccumulation of dangerous radionuclides such as cesium-134 and cesium-137, significantly reducing contamination in the food chain. In German-speaking countries and Scandinavia, this compound became known as Giese salt after Werner Giese, the veterinarian and physicist who pioneered its application after Chernobyl. This article examines the chemistry of this remarkable compound and its classification among Prussian blue compounds, the role of radiocesium in the ecosystem, food safety and agricultural countermeasures, the history and applications of Giese salt in veterinary medicine such as powder, lickstones, and granulates, and its vital role in mitigating one of the worst nuclear disasters in history.

Results:

https://doi.org/10.1007/s40828-025-00217-3

Funding: MJFF, 465.000 EUR

Project Details:
Study Rationale: Parkinson’s disease (PD) is a complex neurodegenerative disorder marked by the loss of dopaminergic neurons, however the underlying exact reasons are still not fully understood. Current treatments focus on alleviating some of the symptoms of the disease, but do not stop disease progression. ACT-02, a new drug developed by Accure Therapeutics, offers a more comprehensive approach by addressing several key aspects of PD, such as alpha-synuclein aggregation, oxidative stress (cell respiration dysfunction) and inflammation. This multi-target strategy not only impacts on slowing disease progression but also improves motor and non-motor symptoms at the same time, offering new hope for managing PD more effectively.

Hypothesis: We hypothesize that inhibition of prolyl endopeptidase (PREP), an enzyme involved in protein aggregation and oxidative stress among other hallmarks of PD, will prevent neuronal death. ACT-02 treatment is expected to simultaneously improve motor and non-motor symptoms while slowing down disease progression, offering a comprehensive therapeutic approach for the treatment of PD.

Study Design: We aim to extend the tissue analysis and validate biomarkers in existing serum and brain tissue samples from transgenic animals (line 61; a reference model of PD), where we previously showed clear improvement of motor and non-motor symptoms, as well a decrease in α-synuclein aggregation and neuroinflammation, after short (1-month) ACT-02 treatment. These promising results support the design of a second efficacy study to assess the impact of longer/term ACT-02 treatment, to support phase II clinical trials. Simultaneously, we plan to complete the remaining experiments required for filing the Investigational New Drug (IND) to enable the Phase I clinical trial within the next 12 months.

Impact on Diagnosis/Treatment of Parkinson’s disease: The ACT-02 program offers a unique and distinct approach for PD treatment by targeting multiple pathways involved in the disease. ACT-02 treatment allows to slow disease progression and address both motor and non-motor symptoms, offering a broader strategy compared to therapies that focus on only one pathway.

Next Steps for Development: Having completed most of the regulatory and proof-of-concept pre-clinical studies required to reach first-in-human trials already, with support from the MJFF we aim to bring ACT-02 to the clinic within 12 months. Additional funding is needed to test the new formulation prototype and conduct longer efficacy study to support a Phase II clinical trial.

Cooperation Partners:

Accure Therapeutics

Funding: Biotech, 260.000 EUR

Project Details:
development of novel treatments