The company, which has an antibody that targets GM-CSF in preclinical development, said in a presentation at the European Congress of Rheumatology that neutralization of the cytokine 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 the 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, which 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.
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.