Study Supports Neutralization of GM-CSF as Novel Therapeutic Approach in Arthritis
Carlsbad, CA - June 27, 2006 - Micromet, Inc. (NASDAQ: MITI), a transatlantic biopharmaceutical company focused on the development of antibody-based drugs, reports results of a scientific study (1) recently presented at the European Congress of Rheumatology in Amsterdam, The Netherlands. The study supports that GM-CSF may represent a promising novel target in arthritis. Moreover, results indicate that neutralization of GM-CSF by an antibody may not only decrease inflammation but also protect cartilage from destruction.
In the study, arthritic mice challenged with streptococcus cell wall fragments were treated with a GM-CSF neutralizing monoclonal antibody (mAB) or with the TNF-alpha blocker etanercept. Compared to the TNF-alpha blocker, the anti-GM-CSF mAB was more potent at decreasing swelling of their affected knee joints. While both mAB and etanercept decreased the number of inflammatory cells in the joints, only the mAB against GM-CSF decreased levels of IL1-beta and reduced proteoglycan loss from the articular knee cartilage.
IL1-beta mediates cartilage and bone destruction via secretion of metalloproteinases and decreases the synthesis of proteoglycan, a main component of articular cartilage, that cushions the joints from wear and tear.
"The results are in full support of our hypothesis that neutralizing GM-CSF is a promising approach for the potential treatment of patients with arthritis," said Patrick Baeuerle, Chief Scientific Officer of Micromet. "It looks as if GM-CSF neutralization could not only reduce inflammation but also protect cartilage from the typical destruction seen in arthritis, and that it might also do so in a situation of TNF-alpha-independent disease."
Micromet has a human antibody against GM-CSF under development. Preclinical results on the candidate, designated MT203, were recently published in Molecular Immunology (2).
GM-CSF was only recently recognized as a key pro-inflammatory cytokine responsible for the proliferation, activation, and survival of a host of immune cells, which play pivotal roles in the development and progression of inflammatory diseases. A significant benefit of neutralizing GM-CSF has been shown in animal models for rheumatoid arthritis, multiple sclerosis, chronic obstructive pulmonary disease, allergic asthma and psoriasis.
References
1) Plater-Zyberk C et al., GM-CSF Neutralization Suppresses Inflammation and Protects Cartilage in Acute Streptococcal Cell Wall Arthritis of Mice, Poster presented at the European Congress of Rheumatology, Amsterdam, The Netherlands, June 2006
2) Krinner, EM et al., A human monoclonal IgG1 potently neutralizing the pro-inflammatory cytokine GM-CSF, Molecular Immunology, May 2006, published electronically ahead of print |
