Product name
Nematode Derived Cystatin Inhibits Allergic Airway Responses and InflammationSummary
A conceptually new biopharmaceutical candidate for the therapy of allergic and inflammatory diseases is offered.Organization name
ipal GmbHProfile
A parasitic nematode derived cystatin (Av17) suppresses allergic airway responsiveness in a murine model of ovalbumin-induced allergy. This was combined with an overall downregulation of effectors of allergic reactions such as IgE, eosinophils and Il-4. Furthermore, the filarial cystatin reduced inflammatory infiltrations and epithelial damage in a murine model of DSS-induced colitis.
Background
Epidemiological studies in humans and experiments in rodent models have consistently shown that infections with parasitic worms lead to reduction of allergic and inflammatory responses.
This manipulation of host immune responses is supposed to help the parasites avoid noxious immune responses, thus ensuring their survival. As a side effect, this worm-induced modulation leads to downregulation of immunopathology resulting from Th2- responses, like allergies and asthma and from Th1-responses, like inflammation induced by viral and bacterial infections.
Clinical trials used swallowed worm eggs as biotherapeutic treatment to cure inflammatory bowel disease (IBD). It was shown that exposure to helminths reduces disease activity in patients with ulcerative colitis or Crohn's disease.
Application: Asthma reduction
The new approach uses recombinant cystatin from parasitic nematodes, especially the filaria Acanthocheilonema viteae.
Reduction of airway hyperreactivity and lung inflammation could be demonstrated by cell number counts, histological analysis and ELISA in a mouse model of ovalbumin (OVA) induced allergic airway hyperresponsiveness.
Application: reduction of colitis
Filarial cystatin inhibits acute and chronic colitis in a Th1-mediated murine model of inflammation.
Acute colitis was induced by DSS-treatment during 7 days. Administration of 4 doses of recombinant Av17 revealed a significant reduction of the inflammatory score (54%).
Similar reduction of the inflammation (63%) could be observed in a chronic colitis model, where animals were treated with DSS over a longer time (4 cycles).
Mechanism of cystatin action
Cystatin targets macrophages via a receptor dependent mechanism. It acts as an immunmodulating secreted protease inhibitor and interferes with allergic responses by modulation of macrophages via the production of IL- 10. This is mediated by a domain of the cell surface receptor CD36 as shown by binding studies in cystatin transfected CHO cells with FITC-stained Anti-CD63 Antibody.
International patent applications have been filed. Additional information is provided in the attached pdf. The technology was developed at the Charité (Berlin/Germany) and is offered by IPAL.
Contact
IPAL GmbH
Dr. Petra Düx
petra.duex(at)ipal.de
About IPAL
The ipal GmbH patent agency assesses and markets the inventions of scientists in the area of Life Sciences and Physics & Engineering from Charité-Universitätsmedizin (University Medicine), Robert Koch Institute, Deutsches Herzzentrum (German Heart Institute), Bundesanstalt für Materialprüfung (BAM - Federal Institute for Materials Research and Testing), the Zuse Institute as well as the Paul Ehrlich Institute, Langen and the Jacobs University Bremen. IPAL provides all of the services necessary - from the assessment of patentable technologies to a comprehensive patent protection all the way to the evaluation of sales returns potentials on the market and successful commercialisation through the use of licensing agreements.
Description File
06045_Cystatin_EX.pdf 06045_Cystatin_Poster.pdf
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