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Researchers at Dresden University Hospital may have discovered a new therapeutic approach for treating myelodysplastic syndromes (MDS). In a recent study, the team headed by Prof. Manja Wobus and Dr. Katja Sockel demonstrated that the anti-inflammatory drug tasquinimod improves blood formation—which is impaired in MDS—and reduces bone damage in preclinical models. Their findings address two central and closely related clinical issues associated with MDS. The corresponding study on the preclinical efficacy of tasquinimod in myelodysplastic syndromes was recently published in the journal “HemaSphere,” a specialist journal for hematology.
MDS, or myelodysplastic neoplasms, are a precursor to leukemia and belong to the group of bone marrow disorders in which the production of healthy blood cells is impaired. This often leads to anemia. At the same time, many patients have an increased risk of osteoporosis, which is attributed to changes in the bone marrow and inflammatory processes.
In their study, the researchers at the National Center for Tumor Diseases (NCT/UCC) in Dresden investigated the effect of tasquinimod, an active ingredient that specifically inhibits inflammatory signaling pathways. “We were able to demonstrate in vitro that the addition of tasquinimod improves the function of key support cells— mesenchymal stromal cells — in the bone marrow and increases the production of red blood cells,” explained Prof. Manja Wobus, first author of the study and group leader in the Laboratory for Experimental Hematology at Medical Clinic 1 (MKI) at the Carl Gustav Carus University Hospital in Dresden. “In addition, an improvement in bone structure was observed in an MDS mouse model, suggesting that the compound could potentially address two key aspects of the disease simultaneously.” Several research groups from the University Hospital Dresden and the Faculty of Medicine at TU Dresden were involved in the successful project.
Thanks to this proof of concept, which was provided by the preclinical study, the researchers' work may now advance to the next phase. The goal is to specifically exploit inflammatory signaling pathways in the bone marrow for therapeutic purposes and to advance the drug into clinical development. From my perspective, this would be the next logical step toward an integrative treatment strategy that takes into account both hematopoiesis and bone health, thereby improving long-term care—especially for patients with low-risk MDS,” says Dr. Katja Sockel, a specialist in internal medicine, hematology, and oncology at the MKI and a clinician-scientist in translational oncology funded by the BMFTR.
The results once again underscore the importance of translational research for advances in the treatment of serious diseases. “Only a precise understanding of inflammatory processes in the bone marrow makes it possible to develop new therapeutic strategies and translate them into clinical practice,” the researchers explain.
“Joint research by a biologist and a physician working in tandem is a model that has proven highly effective in Dresden for tackling complex cancer research projects,” confirms Martin Bornhäuser, Director of the MKI and one of the Executive Directors of the NCT/UCC Dresden. “The NCT/UCC offers ideal conditions for developing new approaches to cancer treatment using state-of-the-art methods, from the laboratory all the way to patient application.”
The study:
Tasquinimod (TASQ) inhibits the inflammatory factor S100A9 and was able to improve impaired blood formation and reduce bone loss in preclinical MDS models. The authors demonstrate that in the bone marrow of MDS patients, neutrophils and macrophages are the primary sources of S100A9 and that TASQ suppresses the resulting inflammatory signaling pathways in mesenchymal stromal cells. Tasquinimod was developed and provided by Active Biotech (Lund, Sweden).
Key findings
• In vitro, TASQ blocked S100A9-mediated activation of TLR4 signaling pathways and reduced inflammatory markers such as IL-1β, IL-18, caspase-1, and PD-L1.
• As a result, the supportive function of mesenchymal stromal cells for hematopoiesis improved; more colony formations of hematopoietic progenitor cells were observed
• Treatment with TASQ increased hemoglobin levels and red blood cell counts in MDS mice, but had no adverse effects in healthy wild-type mice.
• Furthermore, TASQ improved the bone structure, including an increase in trabeculae and bone volume, presumably due to reduced osteoclast activity.
Contact:
Anne-Stephanie Vetter
Staff Unit Public Relations of the Carl Gustav Carus Faculty of Medicine of TUD Dresden University of Technology
National Center for Tumor Diseases (NCT/UCC) Dresden
Tel.: +49 351 458 17903
Email: anne-stephanie.vetter@tu-dresden.de
Prof. Manja Wobus
Medical Clinic 1, Stem Cell Laboratory 2
University Hospital Carl Gustav Carus at TUD Dresden University of Technology
Tel. +49 (0)351 458-14765
E-Mail: manja.wobus@ukdd.de
Manja Wobus et. al, “Preclinical efficacy of tasquinimod in myelodysplastic neoplasms: Restoring erythropoiesis and mitigating bone loss”: http://dx.doi.org/10.1002/hem3.70352.
https://www.nct-dresden.de The Dresden center draws on the structures of the University Cancer Center Dresden (UCC), which was founded in 2003 as one of the first Comprehensive Cancer Centers (CCC) in Germany. Since 2007, the Dresden center has repeatedly been awarded the title of “Oncological Center of Excellence” by the German Cancer Aid (DKH).
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