As of May 20, 2020, the junior research group astacin proteinases started work at the Fraunhofer Institute for Cell Therapy and Immunology IZI. Led by Dr. Daniel Ramsbeck the group is primarily concerned with the design and further development of meprin-Inhibitors and the development of inhibitors of ovastacin. The research group will be funded for almost two years by the investment bank Saxony-Anhalt with funds from the European Regional Development Fund (ERDF).
The actacin family belongs to the proteases, i.e. enzymes that are able to cut bonds between amino acids. Astacins have been found in all living organisms except plants. In humans, the astacins include this bone morphogenetics protein 1 (BMP-1), the meprins α and β, and ovastacin. Findings about the regulation of astacins by activating factors or inhibitors are important, since disturbances in expression or activity can lead to diseases. Meprins in particular have become the focus of drug research in recent years and represent promising target structures for the treatment of kidney diseases, fibrosis - pathological changes in the connective tissue - or even cancer.
The expression of ovastacin could be detected in the ovaries and egg cells, among other things, and is an innovative drug target for the treatment of infertility. Currently, such a treatment is very expensive and requires e.g. B. to hormonal therapy. The approach that the astacin proteinases working group is pursuing together with researchers from Johannes Gutenberg University Mainz, on the other hand, addresses a recently discovered dysregulated mechanism in ovastacin function. The aim is to use this to establish an innovative and non-hormonal treatment option for infertility. In mid-June of this year, the first important findings from the research work were published in the article "Primary evaluation of potential small molecule inhibitors of the astacin metalloproteinase ovastacin, a novel drug target in female infertility treatment" by Hagen Körschgen (Johannes Gutenberg University Mainz), Christian Jäger ( Fraunhofer IZI), Kathrin Tan (Fraunhofer IZI) et al. in the renowned journal ChemMedChem, two: 10.1002/cmdc.202000397.
In addition to research on human proteases, the team around Dr. Ramsbeck also on astacins from parasitic nematodes. The scientists want to develop novel active ingredients for the treatment of worm diseases. These should initially be used in veterinary medicine and then further developed for humans. Of the roundworms that occur practically everywhere, the species occurring in the tropics and subtropics in particular can cause serious diseases in humans. These include, for example, elephantiasis - a severe lymphedema, which is accompanied by massive swelling of the testicles, feet and legs - or blindness. A worldwide increase in resistance makes the development of innovative drugs urgently needed.
The junior research group on astacin proteinases at the Fraunhofer IZI can draw on broad expertise in the field of developing low-molecular active substances, the so-called small molecules. dr Ramsbeck, who has headed the laboratory for medicinal and peptide chemistry at the Molecular Drug Biochemistry and Therapy Development branch office in Halle (Saale) since 2013, explains: "We were in the last phase in the field of inhibitors of astacin proteases, especially meprin α and β years very successfully and have already been able to develop the first highly selective and active inhibitors. We now want to expand this expertise further and apply the know-how we have gained to other proteinases of the astacin family.« In the long term, the employees at the Fraunhofer IZI site in Halle (Saale) want to use this to open up new treatment options. Inhibitors developed by the working group can be further characterized directly on site and tested with regard to their effectiveness, cytotoxicity and other aspects of preclinical drug development.
Source: Fraunhofer IZI press release from June 30.06.2020, XNUMX