Good Reason to Target Receptor Involved in Synovial Inflammation

July 1, 2014

Comparison of inflamed and non-inflamed synovium provide support for targeting a receptor for a molecule that stimulates granulocytes in rheumatoid and psoriatic arthritis.

Greven DEA, Cohen ES, Gerlag DM et al., Extended report: Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis.Ann Rheum Dis (2014) Published Online First: 16 June 2014 doi:10.1136/annrheumdis-2014-205234

Ready your mind to consider another antibody target for rheumatoid arthritis treatment: a receptor for granulocyte macrophage colony stimulating factor (GM-CSF).

The alpha subunit of the receptor, GM-CSFRα, which activates granulocyte immune cells involved in (among many other things) synovial cell overgrowth, is implicated specifically in inflammatory arthritis, these industry-sponsored authors report. Also, targeting it seems to help in a mouse model of the disease.

The number of immune cells positive for GM-CSF receptor α (GM-CSFRα) was greater in RA and PsA patients than in people with OA or healthy controls, the team found when they sampled synovial tissue from 26 patients with active RA, 24 with active PsA, 10 with osteoarthritis and 9 healthy controls. This is the first study to demonstrate this difference between inflammatory and non-inflammatory arthritis, the researchers say, or to find that the molecule is importantly active in the synovium in PsA.

The study also demonstrates that a mouse-tailored version of mavrilimumab, the human antibody against GSM-CSFRα (which doesn't function in rodents), reduced synovial inflammation and joint destruction in a mouse model of arthritis  

The antibody mavrilimumab has shown promising results against RA in Phase II human studies. This research was supported by Medimmune and AstraZenica, the pharmaceutical companies pursuing development of this antibody as a drug.